Ivabradine reversed nondipping heart rate in rats with l‐NAME‐induced hypertension

Abstract

Summary We hypothesized that decreasing elevated night‐time heart rate (HR) in hypertension by administering a bradycardic agent (ivabradine) at bedtime could bring cardiovascular benefit. Since rats are nocturnal animals, they exhibit circadian rhythms phase‐shifted relative to humans. Sixty‐six Wistar rats were divided into non‐diseased controls and rats with l‐NAME‐induced hypertension to compare the haemodynamic effects of daytime‐dosed and night‐time‐dosed ivabradine. l‐NAME‐induced hypertension inverted the physiological 5.6% night‐to‐day HR dip to an undesirable HR rise by 11.1%. Ivabradine dosed at daytime (the rat's resting phase) reverted a night‐to‐day HR rise to HR dip by 14.2%. These results suggest a cardiovascular benefit of ivabradine dosed at the human's resting phase (night‐time) for hypertensive patients with nondipping HR.

Ivabradine Ameliorates Kidney Fibrosis in L-NAME-Induced Hypertension

“…Here, in line with our previous experiments (7,8,34), ivabradine reduced both the average SBP and HR, which indeed might have contributed to the renoprotection. The HR reduction by L-NAME found in this study is consistent with previous results in L-NAME-hypertension by our laboratory (7,8,15) and others (35,36). Several plausible mechanisms of heart rate reduction in L-NAME-hypertension were suggested, including the baroreceptor-mediated modulation of the autonomic nervous system (37,38) and the direct effect of NO-deficiency on cardiac function (39,40).…”

“…Presumably, HR-reduction by ivabradine may be renoprotective via diminishing the hemodynamic burden by both the rate-pressure working product decline and vascular shear stress modulation (33). Here, in line with our previous experiments (7,8,34), ivabradine reduced both the average SBP and HR, which indeed might have contributed to the renoprotection. The HR reduction by L-NAME found in this study is consistent with previous results in L-NAME-hypertension by our laboratory (7,8,15) and others (35,36).…”

“…The HR-reducing effect of ivabradine was declared the principle mechanism of its therapeutic benefit. However, several of ivabradine's pleiotropic effects have recently emerged, which suggests the possibility of using ivabradine in yet off-label indications such as endothelial dysfunction (6), hypertensive heart disease (7), and hypertension with elevated or non-dipping HR (8,9).…”

Monitoring Non-dipping Heart Rate by Consumer-Grade Wrist-Worn Devices: An Avenue for Cardiovascular Risk Assessment in Hypertension

“…Population-based data on nondipping HR (or rising HR) at bedtime may not only improve the pathophysiological understanding of this phenomenon but also show its prognostic value in cardiovascular and even other pathologies, thus rendering non-dipping HR a risk factor and marker of prognosis. Finally, data gathered by wearable devices could help to develop a well-tailored therapeutic approach targeting non-dipping HR (1,3,45,46).…”

Hypertension chronotherapy: does dosing antihypertensive medication at bedtime determine cardiovascular prognosis?

“…Predpokladá sa, že selektívnym znížením nočnej SF (a podporou dippingu SF) by sa dosiahol aditívny KVS benefit pri manažmente hypertenzie (28,29).…”