Displaying publications 1 - 20 of 66 in total

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  1. Fulltext Successful liver transplantation in hepatopulmonary syndrome – case report
    Kam, Choy Chen, Lim, Chooi Bee
    Malaysian Journal of Paediatrics and Child Health, 2016;22(101):0-0.
    MyJurnal
    Hepatopulmonary syndrome (HPS) is characterized by the triad of liver disease, pulmonary vascular dilatation and arterial oxygenation abnormality. It occurs in 4% to 47% in patient with liver cirrhosis [1]. We describe 2 cases of HPS with recovery from hypoxaemia after liver transplantation.(Copied from article)
    Matched MeSH terms: Vasodilation
  2. Fulltext Mitochondrial DNA integrity and function are critical for endothelium-dependent vasodilation in rats with metabolic syndrome
    Kiyooka T, Ohanyan V, Yin L, Pung YF, Chen YR, Chen CL, et al.
    Basic Res Cardiol, 2022 Jan 17;117(1):3.
    PMID: 35039940 DOI: 10.1007/s00395-021-00908-1
    Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10-3 M) compared to Zucker Lean rats (ZLN, 98 ± 11%). This reduction in dilation occurred concomitantly with mitochondrial DNA (mtDNA) strand lesions and reduced mitochondrial complex activities in the endothelium of ZOF versus ZLN. To demonstrate endothelial dysfunction is linked to impaired mitochondrial function, administration of a cell-permeable, mitochondria-directed endonuclease (mt-tat-EndoIII), to repair oxidatively modified DNA in ZOF, restored mitochondrial function and vasodilation to Ach (94 ± 13%). Conversely, administration of a cell-permeable, mitochondria-directed exonuclease (mt-tat-ExoIII) produced mtDNA strand breaks in ZLN, reduced mitochondrial complex activities and vasodilation to Ach in ZLN (42 ± 16%). To demonstrate that mitochondrial function is central to endothelium-dependent vasodilation, we introduced (via electroporation) liver mitochondria (from ZLN) into the endothelium of a mesenteric vessel from ZOF and restored endothelium-dependent dilation to vasoactive intestinal peptide (VIP at 10-5 M, 4 ± 3% vasodilation before mitochondrial transfer and 48 ± 36% after transfer). Finally, to demonstrate mitochondrial function is key to endothelium-dependent dilation, we administered oligomycin (mitochondrial ATP synthase inhibitor) and observed a reduction in endothelium-dependent dilation. We conclude that mitochondrial function is critical for endothelium-dependent vasodilation.
    Matched MeSH terms: Vasodilation*
  3. Fulltext A critical review of pharmacological significance of Hydrogen Sulfide in hypertension
    Ahmad A, Sattar MA, Rathore HA, Khan SA, Lazhari MI, Afzal S, et al.
    Indian J Pharmacol, 2015 May-Jun;47(3):243-7.
    PMID: 26069359 DOI: 10.4103/0253-7613.157106
    In the family of gas transmitters, hydrogen sulfide (H2S) is yet not adequately researched. Known for its rotten egg smell and adverse effects on the brain, lungs, and kidneys for more than 300 years, the vasorelaxant effects of H2S on blood vessel was first observed in 1997. Since then, research continued to explore the possible therapeutic effects of H2S in hypertension, inflammation, pancreatitis, different types of shock, diabetes, and heart failure. However, a considerable amount of efforts are yet needed to elucidate the mechanisms involved in the therapeutic effects of H2S, such as nitric oxide-dependent or independent vasodilation in hypertension and regression of left ventricular hypertrophy. More than a decade of good repute among researchers, H2S research has certain results that need to be clarified or reevaluated. H2S produces its response by multiple modes of action, such as opening the ATP-sensitive potassium channel, angiotensin-converting enzyme inhibition, and calcium channel blockade. H2S is endogenously produced from two sulfur-containing amino acids L-cysteine and L-methionine by the two enzymes cystathionine γ lyase and cystathionine β synthase. Recently, the third enzyme, 3-mercaptopyruvate sulfur transferase, along with cysteine aminotransferase, which is similar to aspartate aminotransferase, has been found to produce H2S in the brain. The H2S has interested researchers, and a great deal of information is being generated every year. This review aims to provide an update on the developments in the research of H2S in hypertension amid the ambiguity in defining the exact role of H2S in hypertension because of insufficient number of research results on this area. This critical review on the role of H2S in hypertension will clarify the gray areas and highlight its future prospects.
    Matched MeSH terms: Vasodilation/physiology
  4. Vasorelaxant effect of 5,7,4'- Trihydroxyflavanone (Naringenin) via endothelium dependent, potassium and calcium channels in Sprague Dawley rats: Aortic ring model
    Tan CS, Tew WY, Jingying C, Yam MF
    Chem Biol Interact, 2021 Oct 01;348:109620.
    PMID: 34411564 DOI: 10.1016/j.cbi.2021.109620
    Naringenin is a naturally occurring flavanone (flavonoid) known to have bioactive effects on human health. It has been reported to show cardiovascular effects. This study aimed to investigate the possible vasorelaxant effect of naringenin and the mechanism behind it by using a Sprague Dawley rat aortic ring assay model. Naringenin caused significant vasorelaxation of endothelium-intact aortic rings precontracted with phenylephrine (pD2 = 4.27 ± 0.05; Rmax = 121.70 ± 4.04%) or potassium chloride (pD2 = 4.00 ± 0.04; Rmax = 103.40 ± 3.82%). The vasorelaxant effect decreased in the absence of an endothelium (pD2 = 3.34 ± 0.10; Rmax = 62.29 ± 2.73%). The mechanisms of the vasorelaxant effect of naringenin in the presence of antagonists were also investigated. Indomethacin, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, atropine, 4-aminopyridine, Nω-nitro-l-arginine methyl ester, glibenclamide and propranolol significantly reduced the relaxation stimulated by naringenin in the presence of endothelium. Besides that, the effect of naringenin on the voltage-operated calcium channel (VOCC) in the endothelium-intact aortic ring was studied, as was intracellular Ca2+ release from the sarcoplasmic reticulum (SR) in the endothelium-denuded aortic ring. The results showed that naringenin also significantly blocked the entry of Ca2+ via the VOCC, SERCA/SOCC and suppressed the release of Ca2+ from the SR. Thus, the vasorelaxant effect shown by naringenin mostly involve the COX pathway, the endothelium-dependent pathway via NO/sGC/prostaglandin, calcium and potassium channels.
    Matched MeSH terms: Vasodilation/drug effects
  5. Characterizing the mechanisms of insulin vasodilatation of normal and streptozotocin-induced diabetic rat aorta
    Subramaniam G, Achike FI, Mustafa MR
    J Cardiovasc Pharmacol, 2009 Apr;53(4):333-40.
    PMID: 19295443 DOI: 10.1097/FJC.0b013e31819fd4a7
    The mechanism by which insulin causes vasodilatation remains unclear, so we explored this in aortic rings from normal Wistar Kyoto and streptozotocin-induced diabetic rats. Insulin-induced relaxation of phenylephrine-contracted [endothelium (ED) intact or denuded] aortic rings was recorded in the presence or absence of various drug probes. Insulin relaxant effect was more in ED-intact than in-denuded tissues from normal or diabetic rats. l-NAME or methylene blue partially inhibited insulin effect in ED-intact but not the ED-denuded tissues, whereas indomethacin (cyclooxygenase inhibitor) had no effect on any of the tissues, indicating that insulin induces relaxation by ED-dependent and -independent mechanisms, the former via the NOS-cyclic guanosine monophosphate but not the cyclooxygenase pathway. The voltage-dependent K channel (KV) blocker (4-aminopyridine) inhibited insulin action in all the tissues (normal or diabetic, with or without ED), whereas the selective BKCa blocker, tetraethylammonium, inhibited it in normal (ED intact or denuded) but not in diabetic tissues, indicating that KV mediates insulin action in normal and diabetic tissues, whereas the BKCa mediates it only in normal tissues, with possible pathophysiologic absence in diabetic tissues. The inward rectifier K channel (Kir) blocker (barium chloride) significantly inhibited insulin effect only in ED-intact or -denuded diabetic tissues, whereas the KATP channel blocker, glibenclamide, inhibited it only in the ED-denuded diabetic tissues, suggesting that Kir channels mediate insulin-induced relaxation in ED-intact or -denuded diabetic tissues, whereas the KATP channel mediates it in ED-denuded diabetic tissues. All the agents combined did not abolish insulin action, suggestive of a direct vasodilatory effect. In conclusion, insulin causes vasodilatation in normal and diabetic tissues via ED-dependent and -independent mechanisms differentially modulated by K channels, some of which functions are altered in diabetes and thus are potential therapeutic targets.
    Matched MeSH terms: Vasodilation/drug effects*; Vasodilation/physiology
  6. Vasorelaxation effect of Glycyrrhizae uralensis through the endothelium-dependent Pathway
    Tan CS, Ch'ng YS, Loh YC, Zaini Asmawi M, Ahmad M, Yam MF
    J Ethnopharmacol, 2017 Mar 06;199:149-160.
    PMID: 28161542 DOI: 10.1016/j.jep.2017.02.001
    ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis (G. uralensis) is one of the herbs used in traditional Chinese medicine (TCM) and serves as an envoy medicinal. Since G. uralensis plays a major role in the anti-hypertensive TCM formulae, we believe that G. uralensis might possess vasorelaxation activity.

    AIM OF THE STUDY: This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect.

    MATERIALS AND METHODS: The vasorelaxation effect of G. uralensis extracts were evaluated on thoracic aortic rings isolated from Sprague Dawley rats.

    RESULTS: Among these three extracts of G. uralensis, 50% ethanolic extract (EFG) showed the strongest vasorelaxation activity. EFG caused the relaxation of the aortic rings pre-contracted with phenylephrine either in the presence or absence of endothelium and pre-contracted with potassium chloride in endothelium-intact aortic ring. Nω-nitro-L-arginine methyl ester, methylene blue, or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one inhibit the vasorelaxation effect of EFG in the presence of endothelium. On the other hand, in the presence of the potassium channel blockers (tetraethylammonium and barium chloride), the vasorelaxation effect of EFG was not affected, but glibenclamide and 4-aminopyridine did inhibit the vasorelaxation effect of EFG. With indomethacin, atropine and propranolol, the vasorelaxation effect by EFG was significantly reduced. EFG was also found to be effective in reducing Ca(2+) release from sarcoplasmic reticulum and the blocking of calcium channels.

    CONCLUSIONS: The results obtained suggest that EFG is involved in the NO/sGC/cGMP pathway.

    Matched MeSH terms: Vasodilation/drug effects*; Vasodilation/physiology
  7. Fulltext Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism
    Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.
    Pharm Biol, 2017 Dec;55(1):2083-2094.
    PMID: 28832263 DOI: 10.1080/13880209.2017.1357735
    CONTEXT: Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia.

    OBJECTIVE: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint.

    MATERIALS AND METHODS: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists.

    RESULTS: The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC50 0.971 ± 0.459 mg/mL), methylene blue (EC50 1.203 ± 0.426 mg/mL), indomethacin (EC50 2.128 ± 1.218 mg/mL), atropine (EC50 0.470 ± 0.325 mg/mL), and propranolol (EC50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca2+ released from the sarcoplasmic reticulum and blocking calcium channels.

    CONCLUSIONS: The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI2 signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β2-adrenergic receptor levels.

    Matched MeSH terms: Vasodilation/drug effects*; Vasodilation/physiology
  8. Concise synthesis of the vasorelaxant alkaloids schwarzinicines A and B
    Lee FK, Krishnan P, Muhamad A, Low YY, Kam TS, Ting KN, et al.
    Nat Prod Res, 2021 Mar 22.
    PMID: 33749454 DOI: 10.1080/14786419.2021.1903005
    A concise synthesis of the 1,4-diarylbutanoid-phenethylamine alkaloids, schwarzinicines A (1) and B (2), recently isolated from Ficus schwarzii, is reported. Key steps include a Claisen condensation to assemble the 1,4-diaryl-2-butanone intermediate, followed by a reductive amination to furnish the core skeleton of the target compounds. The overall synthetic yields of 1 and 2 were 9.1% and 3.5%, respectively. Synthetic (-)-1, (+)-1 and (±)-1 exhibited comparable vasorelaxation as natural schwarzinicine A on rat isolated aortic rings, suggesting that the observed vasorelaxant effects were not influenced by the chirality at C-2.
    Matched MeSH terms: Vasodilation
  9. Fulltext Method optimization on the process of Iontophoresis with laser doppler fluximetry in the assessment of microvascular endothelial function
    Belqes Abdullah, A. T., Yvonne, T. G. B., Ahmad, S. H., Abdul Aziz, A. S. I., Aida, H. G. R.
    Malaysian Journal of Medicine and Health Sciences, 2011;7(1):35-40.
    MyJurnal
    Introduction: Iontophoresis of vasoactive substances such as acetylcholine (ACh) and sodium nitroprusside (SNP) combined with Laser Doppler fluximetry (LDF) is a non-invasive tool used to determine microvascular endothelial function. This study aims to test the effect of sodium chloride on
    non-specific vasodilatation when used as a vehicle in the process of iontophoresis. This study also aims to define the number of current pulses needed to get the maximum effect during iontophoresis with ACh and SNP using low current strength. Methods: The experiment was conducted in five healthy females. Baseline skin perfusion was taken before administration of seven current pulses. Current strength of 0.007 mA and current density of 0.01 mA/cm2 were used. Acetylcholine was used to assess endothelial dependent vasodilatation, while SNP was used to assess endothelial independent vasodilatation. The mean skin perfusion (AU) responses to the iontophoresis of ACh at the anodal and SNP at the cathode leads were recorded. Sodium chloride (0.9%) was used as a vehicle to obtain concentration of 1% for both ACh and SNP. Iontophoresis of pure vehicle (NaCl) was conducted on a separate day to observe the effect of vehicle only on the iontophoresis process at both anode and cathode. Results: Iontophoresis of NaCl showed no significant increase in perfusion compared to baseline at both anode and cathode. Significant increases in skin perfusion were observed with SNP and ACh; a plateau of ACh was reached from the 3rd pulse onwards; while the plateau of SNP was reached from the 4th pulse onwards. Conclusion: NaCl could be used as a vehicle for Ach and SNP during iontophoresis as it did not cause non-specific vasodilatation. Using five current pulses are adequate for iontophoresis of ACh and SNP to assess microvascular endothelial function.
    Matched MeSH terms: Vasodilation
  10. Fulltext The role of reactive oxygen species in pressure-dependent myogenic tone
    Satirah Zainalabidin, Coats, Paul, Wadsworth, Roger M.
    Jurnal Sains Kesihatan Malaysia, 2012;10(1):1-11.
    MyJurnal
    Myogenic tone is the response of the vascular smooth muscle to an increase in intraluminal pressure with vasoconstriction and with vasodilation when the pressure is decreased. Such myogenic tone contributes a level of physiological basal tone in response to neurohumoral stimuli. In spite of myogenic tone discovery by Sir William Bayliss 100 years ago, questions still remain regarding the underlying signaling mechanism of the myogenic response. Studies have shown that increased intraluminal pressure or wall tension leads to membrane depolarization, voltage-operated calcium channel (VOCC), stretch-activated cation (SAC) channels, extracelullar matrix (ECM) and actin cytoskeleton. Recently, evidence has shown a potential role for reactive oxygen species (ROS) as a key signalling mediator in the genesis of myogenic tone. The identification of the primary mechanosensors in the initiation of pressure-dependent myogenic tone is essential as these components could be potential therapeutical targets in the future.
    Matched MeSH terms: Vasodilation
  11. Fulltext Lancifoliaine, a new bisbenzylisoquinoline from the bark of Litsea lancifolia
    Sulaiman SN, Mukhtar MR, Hadi AH, Awang K, Hazni H, Zahari A, et al.
    Molecules, 2011 Apr 13;16(4):3119-27.
    PMID: 21490559 DOI: 10.3390/molecules16043119
    A new bisbenzylisoquinoline, lancifoliaine (1), together with seven known alkaloids--N-allyllaurolitsine (2), reticuline (3), actinodaphnine, norboldine, pallidine, cassythicine and boldine--were isolated from the stem bark of Litsea lancifolia (Lauraceae). In addition to that of lancifoliaine, complete ¹³C-NMR data of N-allyl-laurolitsine (2) was also reported. The alkaloidal structures were elucidated by means of high field 1D- and 2D-NMR IR, UV, and LCMS-IT-TOF spectral data. N-Allyllaurolitsine (2) showed a moderate vasorelaxant activity on isolated rat aorta.
    Matched MeSH terms: Vasodilation/drug effects
  12. Could hypertension possibly be adaptive?
    Prakash ES, Fink GD
    Clin Exp Pharmacol Physiol, 2010 Feb;37(2):e99-e106.
    PMID: 19719749 DOI: 10.1111/j.1440-1681.2009.05284.x
    1. We believe that the ultimate goal of cardiovascular regulatory mechanisms is not the regulation of arterial blood pressure (BP), but the maintenance of tissue blood flows commensurate with metabolic requirements. Thus, elevated BP can potentially contribute to optimizing tissue blood flows under select circumstances; for example, when there are primary defects in autoregulation of tissue blood flows. 2. The hypothesis that a primary defect in autoregulation of tissue blood flows may be responsible for the development of hypertension is presented. It is argued that, in this context, at least part of the rise in BP may be reflexly driven by a 'metaboreflex', a homeostatic mechanism acting to regulate tissue blood flows. 3. We argue that in the context of primary defects in autoregulation of tissue blood flows, the ability to generate and sustain a hypertensive phenotype increases the lifespan of species (i.e. if it were not for this adaptive hypertensive phenotype, death due to circulatory failure would occur much earlier). 4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested.
    Matched MeSH terms: Vasodilation/physiology
  13. Mechanisms of action of Panax notoginseng ethanolic extract for its vasodilatory effects and partial characterization of vasoactive compounds
    Loh YC, Tan CS, Ch'ng YS, Ng CH, Yeap ZQ, Yam MF
    Hypertens Res, 2019 02;42(2):182-194.
    PMID: 30464217 DOI: 10.1038/s41440-018-0139-9
    Panax notoginseng is the most valuable medicinal plant and has been used clinically for more than two thousand years to treat various diseases, including hypertension. Previous studies claimed that different isolated compounds from P. notoginseng are involved in different pathways for vasodilation. It is strongly believed that these vasodilating compounds might act synergistically in contributing vasodilatory effects via holistic signaling pathways. The present study aims to evaluate the vasodilatory effect and mechanism of action employed by the crude extract of P. notoginseng. The fingerprint of P. notoginseng was developed using tri-step FTIR and HPTLC. The contents of Rg1 and Rb1 in the active extract (PN95) were further quantified via HPTLC. The vasodilatory effect of PN95 was evaluated using an in vitro aortic ring model. The results showed that PN95 contains a high amount of Rg1 and Rb1, 25.9 and 13.6%, respectively. The vasodilatory effect of PN95 was elicited via the NO/sGC/cGMP and β2-adrenergic receptors pathways. Furthermore, PN95 could manage vascular tone by regulating action potentials via potassium and both VOCC and IP3R pathways. The results obtained fulfilled the expected outcome where the PN95 employed more signaling pathways than any of the single active compounds; hence, the holistic therapeutic effect could be achieved and would more easily translate to applications for the treatment of human diseases.
    Matched MeSH terms: Vasodilation/drug effects*
  14. Mechanism of vasorelaxation induced by eupatorin in the rats aortic ring
    Yam MF, Tan CS, Ahmad M, Shibao R
    Eur J Pharmacol, 2016 Oct 15;789:27-36.
    PMID: 27370961 DOI: 10.1016/j.ejphar.2016.06.047
    Previous studies demonstrated that eupatorin content in Orthosiphon stamineus fractions correlated with their vasorelaxation activity. Even with previous studies, there is still very little information on the vasorelaxation effect of eupatorin, and not many scientific studies had been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of eupatorin. The vasorelaxation activity and the underlying mechanisms of eupatorin was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. Eupatorin caused the relaxation of aortic rings pre-contracted with phenylephrine with and without endothelium (pD2=6.66±0.13, EMAX=99.72±6.39%; pD2=6.10±0.22, EMAX=65.78±8.01%), and also the relaxation of endothelium-intact aortic rings pre-contracted with potassium chloride (pD2=6.20±0.30, EMAX=71.89±12.25%). In the presence of Nω-nitro-l-arginine methyl ester (pD2<4.60, EMAX=24.91±6.39%), methylene blue (pD2=6.05±0.38, EMAX=66.79±9.69%), ODQ (pD25.84±0.32, EMAX=60.47±9.6%), indomethacin (pD2=6.27±0.21, EMAX=76.03±9.45%), tetraethylammonium (pD2=6.09±0.35, EMAX=69.35±11.31%), 4-aminopyridine (pD2=6.34±0.12, EMAX=76±6.1%), barium chloride (pD2=6.47±0.14, EMAX=79.61±10.02%), atropine (pD2=6.36±0.29, EMAX=86.47±12.95%) and propranolol (pD2=6.49±0.26, EMAX=83.2±12.01%), relaxation stimulated by eupatorin was significantly reduced. Eupatorin was also found to be active in reducing Ca(2+) release from sarcoplasmic reticulum and in blocking calcium channels. The present study demonstrates the vasorelaxation effect of eupatorin involving NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors.
    Matched MeSH terms: Vasodilation/drug effects*
  15. Fulltext Evaluation of vasodilatory effect and antihypertensive effect of chrysin through in vitro and sub-chronic in vivo study
    Tew WY, Tan CS, Yan CS, Loh HW, Wen X, Wei X, et al.
    Biomed Pharmacother, 2023 Jan;157:114020.
    PMID: 36469968 DOI: 10.1016/j.biopha.2022.114020
    Chrysin, a bioflavonoid belonging to the flavone, occurs naturally in plants such as the passionflower, honey and propolis. Few studies have demonstrated that chrysin can promote vasorelaxant activities in rats' aorta and mesenteric arteries. To date, no research has explored the signalling system routes that chrysin may utilise to produce its vasorelaxant action. Therefore, this study aimed to investigate the underlying mechanisms involved in chrysin-induced vasorelaxant in rats' aortic rings and assess the antihypertensive effect of chrysin in spontaneously hypertensive rats (SHRs). The findings revealed that chrysin utilised both endothelium-dependent and endothelium-independent mechanisms. The presence of L-NAME (endothelial NO synthase inhibitor), ODQ (sGC inhibitor), methylene blue (cGMP lowering agent), 4-AP (voltage-gated potassium channel inhibitor), atropine (muscarinic receptors inhibitor) and propranolol (β-adrenergic receptors inhibitor) significantly reduced the chrysin's vasorelaxant action. Furthermore, chrysin can reduce intracellular Ca2+ levels by limiting the extracellular intake of Ca2+ through voltage-operated calcium channels and blocking the intracellular release of Ca2+ from the sarcoplasmic reticulum via the IP3 receptor. These indicate that chrysin-induced vasorelaxants involved NO/sGC/cGMP signalling cascade, muscarinic and β-adrenergic receptors, also the potassium and calcium channels. Although chrysin had vasorelaxant effects in in vitro studies, the in vivo antihypertensive experiment discovered chrysin does not significantly reduce the blood pressure of SHRs following 21 days of oral treatment. This study proved that chrysin utilised multiple signalling pathways to produce its vasorelaxant effect in the thoracic aorta of rats; however, it had no antihypertensive effect on SHRs.
    Matched MeSH terms: Vasodilation*
  16. Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta
    Machha A, Mustafa MR
    J Cardiovasc Pharmacol, 2005 Jul;46(1):36-40.
    PMID: 15965352
    Flavonoids are known to possess cardioprotective properties. Vascular endothelial function is a surrogate marker for cardiovascular diseases, including hypertension. We have studied the effects of chronic flavonoid treatment on vascular endothelial functions in spontaneously hypertensive rats (SHR). Starting from 6-7 weeks old, SHR were given flavonoids (baicalein, flavone, or quercetin) orally (10 mg/kg, once daily) to the SHRs for 4 weeks. Aortas from all the flavonoid-treated animals showed remarkably higher endothelium-dependent relaxations to acetylcholine, to a similar extent as those pretreated with the angiotensin-converting enzyme inhibitor, captopril. However, in contrast to other experimental groups, flavone pretreatment also enhanced the endothelium-independent relaxations to sodium nitroprusside. In addition, treatment with either flavone or quercetin induced a significant attenuation in systolic blood pressure of the hypertensive animals. The present results suggest that chronic treatment with the flavonoids (baicalein, flavone, and quercetin) preserves vascular endothelial functions in hypertensive animals through several possible actions, including increasing endothelial nitric oxide production and bioavailability and reduction in blood pressure.
    Matched MeSH terms: Vasodilation/drug effects; Vasodilation/physiology
  17. Fulltext Co-administration of conjugated linoleic acid and rosiglitazone increases atherogenic co-efficient and alters isoprenaline-induced vasodilatation in rats fed high fat diet
    Chai BK, Lau YS, Loong BJ, Rais MM, Ting KN, Dharmani DM, et al.
    Physiol Res, 2018 Nov 14;67(5):729-740.
    PMID: 29750886
    The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (R(max)=53+/-4.7 %; pEC50=6+/-0.2) compared to endothelium-intact aortas (R(max)=100+/-9.9 %; pEC50=7+/-0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.
    Matched MeSH terms: Vasodilation/drug effects; Vasodilation/physiology*
  18. Antihypertensive activity and vascular reactivity mechanisms of Vitex pubescens leaf extracts in spontaneously hypertensive rats
    Al-Akwaa AA, Asmawi MZ, Dewa A, Mahmud R
    Heliyon, 2020 Jul;6(7):e04588.
    PMID: 32775735 DOI: 10.1016/j.heliyon.2020.e04588
    Background: Vitex pubescens has been used traditionally in hypertension treatment but not yet scientifically assessed. The objective of the study is to investigate the antihypertensive and vasorelaxant activities of V. pubescens, study its underlying pharmacological mechanisms, and identify the relevant vasoactive compounds.

    Methods: Successive extractions of V. pubescens leaf were carried out to produce petroleum ether (VPPE), chloroform (VPCE), methanol (VPME), and water (VPWE) extracts. Spontaneously hypertensive rats (SHRs) received a daily oral administration of the extracts (500 mg/kg/day; n = 6) or verapamil (15 mg/kg/day; n = 6) for 2 weeks, while the systolic and diastolic blood pressures were measured using non-invasive tail-cuff method. Vasorelaxation assays of the extracts were later conducted using phenylephrine (PE, 1 μM) pre-contracted aortic ring preparation. Mechanisms of vasorelaxation by the most potent fraction were studied using vasorelaxation assays with selected blockers/inhibitors. GC-MS was conducted to determine the active compounds.

    Results: VPPE elicited the most significant diminution in systolic and diastolic blood pressure of treated SHRs and produced the most significant vasorelaxation in the aortic rings. Vasorelaxant effects of F2-VPPE were significantly reduced in endothelium-denuded aortic rings by glibenclamide (1 μM), whereas calcium chloride and PE-induced contractions were significantly suppressed. Endothelium removal of the aortic rings or incubation with indomethacin (10 μM), atropine (1 μM), methylene blue (10 μM), propranolol (1μM) and L-NAME (10 μM) did not significantly alter F2-VPPE-induced vasorelaxation. Seven compounds were identified using GC-MS, including spathulenol.

    Conclusion: F2-VPPE exerted its endothelium-independent vasorelaxation by inhibition of vascular smooth muscle contraction induced by extracellular Ca+2 influx through trans-membrane Ca+2 channels and/or Ca+2 release from intracellular stores, and by activation of KATP channels. The vasorelaxation effects of V. pubescens could be mediated by the compound, spathulenol.

    Matched MeSH terms: Vasodilation
  19. Fulltext Overview of the Microenvironment of Vasculature in Vascular Tone Regulation
    Loh YC, Tan CS, Ch'ng YS, Yeap ZQ, Ng CH, Yam MF
    Int J Mol Sci, 2018 Jan 02;19(1).
    PMID: 29301280 DOI: 10.3390/ijms19010120
    Hypertension is asymptomatic and a well-known "silent killer", which can cause various concomitant diseases in human population after years of adherence. Although there are varieties of synthetic antihypertensive drugs available in current market, their relatively low efficacies and major application in only single drug therapy, as well as the undesired chronic adverse effects associated, has drawn the attention of worldwide scientists. According to the trend of antihypertensive drug evolution, the antihypertensive drugs used as primary treatment often change from time-to-time with the purpose of achieving the targeted blood pressure range. One of the major concerns that need to be accounted for here is that the signaling mechanism pathways involved in the vasculature during the vascular tone regulation should be clearly understood during the pharmacological research of antihypertensive drugs, either in vitro or in vivo. There are plenty of articles that discussed the signaling mechanism pathways mediated in vascular tone in isolated fragments instead of a whole comprehensive image. Therefore, the present review aims to summarize previous published vasculature-related studies and provide an overall depiction of each pathway including endothelium-derived relaxing factors, G-protein-coupled, enzyme-linked, and channel-linked receptors that occurred in the microenvironment of vasculature with a full schematic diagram on the ways their signals interact. Furthermore, the crucial vasodilative receptors that should be included in the mechanisms of actions study on vasodilatory effects of test compounds were suggested in the present review as well.
    Matched MeSH terms: Vasodilation
  20. Fulltext Role of endothelium-dependent hyperpolarisation and prostacyclin in diabetes
    Mokhtar SS, Rasool AH
    Malays J Med Sci, 2015 Mar-Apr;22(2):8-17.
    PMID: 26023290 MyJurnal
    The endothelium plays a crucial role in maintaining vascular homeostasis by producing several vasodilating factors, including nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarisation (EDH); however, the balance between endothelial relaxing and contracting factors is disrupted in disease states such as diabetes mellitus and hypertension. Most reported studies of endothelial dysfunction in diabetes focused on the actions of NO; however, there is accumulating evidence demonstrating that in addition to NO, PGI2 and EDH are likely to contribute to the vasodilatation of blood vessels. EDH plays an important role as a regulator of vascular tone and reactivity in resistance and conduit arteries of animal models and humans. PGI2 only plays a minimal role in endothelium-dependent vasodilatation but may serve as an important compensatory mechanism in conditions in which NO and EDH activities are decreased. Further studies are needed to determine the exact roles of EDH and PGI2 in the development of endothelial dysfunction and clinical vasculopathy in humans with type 1 and type 2 diabetes.
    Matched MeSH terms: Vasodilation
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