Alterations in Blood Pressure and Heart Rate Variability in Transgenic Rats With Low Brain Angiotensinogen

Abstract

To study whether the brain renin-angiotensin system plays a role in the long-term and short-term control of blood pressure and heart rate variability, we examined in transgenic rats [TGR(ASrAOGEN)] with low brain angiotensinogen levels the 24-hour variation of blood pressure and heart rate. Telemetry recordings were made during basal and hypertensive conditions induced by a low-dose subcutaneous infusion of angiotensin II for 7 days. Short-term blood pressure and heart rate variability were evaluated by spectral analysis, and as a measure of baroreflex sensitivity, the average transfer gain between the pressure and heart rate variations was calculated. During the angiotensin II infusion in control but not TGR(ASrAOGEN) rats, the 24-hour rhythm of blood pressure was inverted (5.8±2 versus −0.4±1.8 mm Hg/group of day-night differences of blood pressure, P <0.05, respectively). In both the control and TGR(ASrAOGEN) rats, the 24-hour heart rate rhythms remained unaltered and paralleled those of locomotor activity. The transfer gain between 0.3 to 0.6 Hz was significantly higher in TGR(ASrAOGEN) than in control rats during control (0.71±0.1 versus 0.35±0.06, P <0.05) but not during angiotensin II infusion (0.6±0.07 versus 0.4±0.1, P >0.05). These results demonstrate that the brain renin-angiotensin system plays an important role in mediating the effects of angiotensin II on the circadian variation of blood pressure. Furthermore, these data indicate that a permanent deficiency in the brain renin-angiotensin system alters the reflex control of heart rate in rats.