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Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation

Khan SA, Sattar MZ, Abdullah NA, Rathore HA, Abdulla MH, Ahmad A, et al.

Acta Physiol (Oxf), 2015 Jul;214(3):390-401.
PMID: 25846561 DOI: 10.1111/apha.12499

AIM:
This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity.

METHODS:
Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load.

RESULTS:
Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats.

CONCLUSION:
Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control.

KEYWORDS:
baroreflex gain curves; cardiopulmonary reflex; high-fat diet

Matched MeSH terms: Baroreflex*
Heart rate variability and baroreflex sensitivity abnormalities in Guillain-Barré syndrome: a pilot study

Tan CY, Shahrizaila N, Yeoh KY, Goh KJ, Tan MP

Clin Auton Res, 2019 06;29(3):339-348.
PMID: 29654380 DOI: 10.1007/s10286-018-0525-z

OBJECTIVE: The current study aimed to investigate autonomic dysfunction in Guillain-Barré syndrome (GBS) patients and describe the results of computational heart rate variability (HRV)/baroreflex sensitivity (BRS) and autonomic challenge tests.
METHODS: GBS patients were consecutively recruited and the results were compared to age- and gender-matched healthy controls. A series of autonomic function tests including computation-dependent tests (power spectrum analysis of HRV and BRS at rest) and challenge maneuvers (deep breathing, eyeball compression, active standing, the Valsalva maneuver, sustained handgrip, and the cold pressor test) were performed.
RESULTS: Ten GBS patients (six men; mean age = 40.1 ± 13.9 years) and ten gender- and age-matched healthy controls were recruited. The mean GBS functional grading scale at disease plateau was 3.4 ± 1.0. No patients required intensive care unit admission or mechanical ventilation. Low-frequency HRV (p = 0.027), high-frequency HRV (p = 0.008), and the total power spectral density of HRV (p = 0.015) were significantly reduced in patients compared to controls. The mean up slope (p = 0.034), down slope (p = 0.011), and total slope (p = 0.024) BRS were significantly lower in GBS patients. The diastolic rise in blood pressure in the cold pressor test was significantly lower in GBS patients compared to controls (p = 0.008).
INTERPRETATION: Computation-dependent tests (HRV and BRS) were more useful for detecting autonomic dysfunction in GBS patients, whereas the cold pressor test was the only reliable challenge test, making it useful as a bedside measure of autonomic function in GBS patients.

Matched MeSH terms: Baroreflex/physiology*
Fulltext Comparison of high-fat style diet-induced dysregulation of baroreflex control of renal sympathetic nerve activity in intact and ovariectomized female rats: Renal sympathetic nerve activity in high-fat style diet fed intact and ovariectomized female rats

Sucedaram Y, Johns EJ, Husain R, Sattar MA, Abdulla M, Khalilpourfarshbafi M, et al.

Exp Biol Med (Maywood), 2020 05;245(9):761-776.
PMID: 32212858 DOI: 10.1177/1535370220915673

IMPACT STATEMENT: Over activation of renal sensory nerve in obesity blunts the normal regulation of renal sympathetic nerve activity. To date, there is no investigation that has been carried out on baroreflex regulation of renal sympathetic nerve activity in obese ovarian hormones deprived rat model, and the effect of renal denervation on the baroreflex regulation of renal sympathetic nerve activity. Thus, we investigated the role of renal innervation on baroreflex regulation of renal sympathetic nerve activity in obese intact and ovariectomized female rats. Our data demonstrated that in obese states, the impaired baroreflex control is indistinguishable between ovarian hormones deprived and non-deprived states. This study will be of substantial interest to researchers working on the impact of diet-induced hypertension in pre- and postmenopausal women. This study provides insight into health risks amongst obese women regardless of their ovarian hormonal status and may be integrated in preventive health strategies.

Matched MeSH terms: Baroreflex/physiology*
Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure

Khan SA, Sattar MA, Rathore HA, Abdulla MH, Ud Din Ahmad F, Ahmad A, et al.

Acta Physiol (Oxf), 2014 Mar;210(3):690-700.
PMID: 24438102 DOI: 10.1111/apha.12237

There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure.

Matched MeSH terms: Baroreflex/physiology*
Fulltext A cardiovascular mathematical model of graded head-up tilt

Lim E, Chan GS, Dokos S, Ng SC, Latif LA, Vandenberghe S, et al.

PLoS One, 2013;8(10):e77357.
PMID: 24204817 DOI: 10.1371/journal.pone.0077357

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

Matched MeSH terms: Baroreflex/physiology
Preclinical safety assessments of nano-sized constructs on cardiovascular system toxicity: A case for telemetry

Cheah HY, Kiew LV, Lee HB, Japundžić-Žigon N, Vicent MJ, Hoe SZ, et al.

J Appl Toxicol, 2017 Nov;37(11):1268-1285.
PMID: 28165137 DOI: 10.1002/jat.3437

While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd.

Matched MeSH terms: Baroreflex/drug effects*
Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

Lozić M, Tasić T, Martin A, Greenwood M, Šarenac O, Hindmarch C, et al.

Pharmacol Res, 2016 12;114:185-195.
PMID: 27810519 DOI: 10.1016/j.phrs.2016.10.024

The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress. Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress. However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology.

Matched MeSH terms: Baroreflex