Autonomic cardiovascular responses to chronic infusions of angiotensin II (ANGII) in wistar kyoto rats (WKY)

Abstract

We hypothesized that the hypertension developed during chronic infusion of ANGII results from elevated sympathetic tone and reduced baroreflex sensitivity. Arterial pressure (AP) and heart rate (HR) were recorded via radio telemetry in WKY rats (10‐11 weeks old) chronically infused with ANGII (50, 200 & 800 ng·kg−1·min−1 s.c. for 10 days). Mean AP increased rapidly in the 800 ng group (91 to 151 mmHg by day 8, p<0.05, n=12; peak response), more gradually in the 200 ng group (88 to 117 mmHg by day 10, p<0.001, n=12) and slowly in the 50 ng group (98 to 104 mmHg by day 10, p<0.05, n=12). HR declined initially, apparently due to the baroreflex, in all 3 groups with magnitude and time scale being dose‐dependent. Increases in the very low frequency spectra of AP in both 200 and 800 ng·kg−1·min−1 groups occurred by day 8 suggesting increased sympathetic tone. The spontaneous baroreflex gain (sBRG) showed time and dose dependent changes: the 800 ng group showed an increase peaking on day 2 before declining by day 8 whereas the 200 ng group showed a delayed and blunted elevation in sBRG peaking on day 7 before declining. Thus, peripheral ANGII alters cardiovascular autonomic function which is delayed relative to the onset of hypertension. We propose that ANGII infusion in normotensive rats is a good model for understanding mechanisms of autonomic dysfunction underpinning the development of hypertension. Supported by BBSRC, Pfizer & BHF.