Effects of vasodilators on beat-to-beat and every fifteen minutes blood pressure variability induced by noradrenaline infusion in rats

Abstract

Increased blood pressure variability (BPV) was shown to be associated with cardiovascular morbidities and/or mortalities. There are various types of BPV depending on time intervals of BP measurements, ranging from beat-to-beat to visit-to-visit or year-to-year. We previously found that continuous infusion of noradrenaline (NA) for 14 days increased short-term BPV every 15 min in rats. The aims of this study were to examine (1) whether NA infusion increases very short-term beat-to-beat BPV, (2) the effects of azelnidipine and hydralazine on NA-induced BPV, and (3) whether baroreceptor reflex sensitivity (BRS) is affected by NA or NA plus those vasodilators. Nine-week-old Wistar rats infused subcutaneously with 30 μg/h NA were orally treated with or without 9.7 mg/day azelnidipine or 5.9 mg/day hydralazine over 14 days. BP levels were continuously monitored via abdominal aortic catheter with a telemetry system in an unrestrained condition. Standard deviations (SDs) were used to evaluate beat-to-beat BPV and BPV every 15 min which was obtained by averaging BP levels for 10-s segment at each time point. BRS was determined by a sequence analysis. Continuous NA infusion over 14 days increased average BP, beat-to-beat BPV, and BPV every 15 min, lowering BRS. Comparing the two vasodilators, hydralazine reduced BP elevation by NA; meanwhile, azelnidipine alleviated BPV augmentation, preserving BRS, despite a smaller BP reduction. Thus, NA infusion increased both very short- and short-term BPV concomitantly with impaired BRS, while azelnidipine had an inhibitory effect, possibly independent of BP-lowering, on those types of BPV and impairment of BRS.