Gender Dependency of Circadian Blood Pressure and Heart Rate Profiles in Spontaneously Hypertensive Rats: Effects of Beta‐Blockers

Abstract

This study investigated (i) blood pressure (BP), heart rate (HR), and their relation to urinary NOx and eNOS protein expression in male and female spontaneously hypertensive rats (SHR), as well as (ii) gender-dependent cardiovascular effects of nebivolol (NEB) in comparison to metoprolol (MET) in SHR. BP and HR were measured telemetrically after a single intraperitoneal application of NEB or MET at 07.00 and 19.00 h in male rats and at 19.00 h in proestrus female rats. The two beta-blockers varied in time of decreasing BP and HR and also in duration. In males, MET decreased BP and HR for few hours exclusively when applied at the onset of the activity phase (i.e., at 19.00 h), while after its application at 07.00 h, BP and HR were unchanged. In females, MET also caused a short-lasting BP and HR reduction, with the effect being more pronounced than in males. In males, NEB at either dosing time decreased HR and BP to a greater extent than did MET. This effect was evident both during the activity and rest periods and persisted for at least five days. In females, NEB provoked a similar, but more pronounced, effect on BP and HR in comparison to males. These findings demonstrate that significant gender-dependent differences in the circadian profile of BP and HR exist. BP and urinary NOx as well as eNOS expression are inversely correlated, and the cardiovascular effects of NEB and MET vary, depending on the time of application as well as gender.

Evidence for an estradiol-agonistic action of nebivolol in spontaneously hypertensive rats

“…In a previous study, we showed that NEB induces a longlasting reduction of blood pressure in SHR [20] that interestingly did not correlate with the NO production.…”

“…at the onset of the dark phase (1900 h). The dosage of 30 mg/kg had been shown to effectively lower blood pressure [20]. 17b-Estradiol was administered i.p.…”

Thromboxane A2 receptor antagonist (ONO‐8809) attenuates renal disorders caused by salt overload in stroke‐prone spontaneously hypertensive rats

“…The data that support the findings of this study are available from the corresponding author, H.H., on reasonable request, and openly available in each repository at reference number [1–46].…”

Persistence of circadian variation in arterial blood pressure in β1/β2-adrenergic receptor-deficient mice

“…Circulating catecholamines are higher in the active phase, during the day in humans and during the night in rodents (4,8). Many pharmacological studies that have compared the effect of administration of ␤-blockers on arterial pressure in different phases of the circadian cycle have demonstrated that the agents produce larger effects in the active phase (9,14). Nevertheless, while we also demonstrated a somewhat greater dark-light difference in arterial pressure between the WT and the genetically "␤ -blocked" animals, the persistence of robust rhythmic variations in pressure and heart rate indicates that there must be other major effector pathways.…”