Systemic hemodynamic effects of chronic intrarenal infusion of angiotensin II: Role of the autonomic nervous system

Angiotensin n (Ang II, 0.5 ng/kg/min) was infused into the left renal artery of dogs (n=6) for 28 days. Hemodynamic variables were measured over 3 pre-infusion days, on days 1, 7, 14, 21 and 28 of this infusion and 1 and 10 days after cessation of infusion. Mean arterial pressure did not change significantly in the first 24 hr of Ang n infusion but increased significantly over days 14-28 (+5.8±1.7 mmHg, P=0.002). Total peripheral resistance (TPR) (+3.9±1.8 mmHg.min/l, P=0.03) and renal vascular resistance (+0.04±0.02 mmHg.min/ml, P=0.03) also increased significantly, while cardiac output tended to decrease (-0.4±0.2 l/min, P=0.08). Central venous pressure and glomerular filtration rate were not significantly changed but hematocrit rose steadily (+6±2 % on day 28 of infusion, P<0.001). The role of the autonomie nervous system in the developing hypertension was studied using acute ganglion blockade (pentolinium; 6 mg/kg and 3 mg/kg/hr, i.v.) before and during (on days 7, 14 and 28) the infusion. Before Ang II infusion, pentolinium reduced TPR (4±2 mmHg.min/l) and increased arterial pressure (11±4 mmHg) and cardiac output (1.0±0.3 l/min). The increases in arterial pressure and cardiac output following pentolinium were progressively greater during the 4 weeks of Ang II infusion and by day 28 were 27±8 mmHg and 1.8±0.5 l/min, (P=0.02 & 0.03, respectively). In summary, long-term infusion of Ang II directly into the renal artery at a low dose produces chronic, stable hypertension mediated by increased TPR. The results indicate that the autonomie nervous system buffers the rise in arterial pressure.