HEMODYNAMIC-EFFECTS OF CENTRAL ANGIOTENSIN-I, ANGIOTENSIN-II, AND ANGIOTENSIN-III IN CONSCIOUS RABBITS

We have examined the hemodynamic effects of intraventricular angiotensins in conscious rabbits. Fourth ventricular injections of angiotensin II (ANG II, 8 fmol to 25 pmol) produced dose-dependent pressor response at doses 400 times less than equipressor intravenous doses. Lateral ventricle administration of doses up to 1,000 pmol had little effect on mean arterial pressure (maximum +7 +/- 3 mmHg, P < 0.05, n = 9). Comparison of dose-response curves to ANG I, II, and III showed that all three had similar maximum pressor effects (27 +/- 3 mmHg), with ANG I being four times less potent than ANG II, and ANG III as potent as ANG II. Central pretreatment with the ANG-converting enzyme inhibitor enalapril abolished the pressor response to ANG I, suggesting that it was mediated entirely through ANG II. Examination of the hemodynamic changes after ANG I, II, and III in rabbits instrumented with aortic, mesenteric, or hindquarter flow probes showed that the rise in blood pressure to all three agents was due entirely to a decrease in total peripheral conductance, since cardiac output and heart rate fell. Peripheral conductance changes were not uniform, with the mesenteric bed showing an average 20 +/- 3% fall in conductance, while the hindquarter conductance increased (+12 +/- 3%). In sinoaortic-denervate rabbits, however, central angiotensins reduced conductance equally in the hindlimb and mesenteric beds, suggesting that the hindlimb dilatation in the baroreceptor intact rabbit was due to baroreflex buffering of the pressor effect. In conclusion, these studies suggest that the main sites for ANG effects on the cardiovascular system are located in the brain stem. The hemodynamic pattern after central ANG I, II, and III consisted of regional vasoconstriction in conjunction with opposing baroreflex effects. This site thus provides a potentially important integrative mechanism for influencing sympathetic vasomotor tone in the rabbit.