Analysis of heart rate (HR) and heart rate variability (HRV) are powerful tools to investigate cardiac diseases, but current methods, including 24-h Holter monitoring, can be cumbersome and may be compromised by movement artefact. A commercially available data capture and analysis system was used in anaesthetised healthy cats to measure HR and HRV during pharmacological manipulation of HR. Seven healthy cats were subjected to a randomised crossover study design with a 7 day washout period between two treatment groups, placebo and atenolol (1mg/kg, IV), with the efficacy of atenolol to inhibit β1 adrenoreceptors challenged by epinephrine. Statistical significance for the epinephrine challenge was set at P<0.0027 (Holm-Bonferroni correction), whereas a level of significance of P<0.05 was set for other variables. Analysis of the continuous electrocardiography (ECG) recordings showed that epinephrine challenge increased HR in the placebo group (P=0.0003) but not in the atenolol group. The change in HR was greater in the placebo group than in the atenolol group (P=0.0004). Therefore, compared to cats pre-treated with placebo, pre-treatment with atenolol significantly antagonised the tachycardia while not significantly affecting HRV. The increased HR in the placebo group following epinephrine challenge was consistent with a shift of the sympathovagal balance towards a predominantly sympathetic tone. However, the small (but not significant at the critical value) decrease in the normalised high-frequency component (HFnorm) in both groups of cats suggested that epinephrine induced a parasympathetic withdrawal in addition to sympathetic enhancement (increased normalised low frequency component or LFnorm). In conclusion, this model is a highly sensitive and repeatable model to investigate HRV in anaesthetised cats that would be useful in the laboratory setting for short-term investigation of cardiovascular disease and subtle responses to pharmacological agents in this species.
Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched spontaneously hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor-mediated contractions induced by phenylephrine (PE) were augmented in diabetic (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/-6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was without any significant effects on the vascular responses to ACh, SNP and PE in aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that observed in normal aortic rings, but this enhancement in ACh-induced relaxations was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid markedly attenuated contractions induced by PE in aortic rings from both SHR (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally, following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid attenuated PE-induced contractions in all aortic ring types studied. These results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor agonists in diabetic arteries is independent of endothelial nitric oxide dysfunction; (2) ascorbic acid directly modulates contractile responses of hypertensive and diabetic rat aortas, likely through mechanisms in part independent of preservation of endothelium-derived nitric oxide.