ACUTE AND CHRONIC ANGIOTENSIN HYPERTENSION - NEURAL AND NONNEURAL COMPONENTS, TIME-COURSE, AND DOSE-DEPENDENCY

We examined the mechanisms mediating hypertension in conscious rats du ring acute and chronic infusion of angiotensin II (ANG II) at pressor doses (50, 100, and 200 ng . kg(-1). min(-1)). Trimethaphan-induced bl ood pressure reduction was inversely related to the acute dose of ANG II, consistent with a constrictor action of ANG II on vascular smooth muscle and withdrawal of sympathetic tone. During chronic ANG II infus ion, the entire increase in mean arterial pressure (MAP) was inhibited by trimethaphan, consistent with neural mediation. During acute ANG I I hypertension, the AT(1)-specific receptor blocker losartan induced a large fall in MAP (64 +/- 4 mmHg) in ganglion-blocked (chlorisondamin e) rats, whereas, during chronic ANG II hypertension, losartan had onl y a small hypotensive effect (11 +/- 3 mmHg). To determine the time co urse of the change from vascular smooth muscle action to neural action , we measured MAP in response to trimethaphan during the first 24 h of ANG II infusion. After 5 h, the minimal MAP in response to trimethaph an was significantly higher than that before ANG II. After 10 h of inf usion, trimethaphan decreased MAP to pre-ANG II levels. That is, the n eural component was fully active after only 10 h of infusion in rats. Finally, chronic administration of ANG II resulted in a dose-related i ncrease in MAP that, at all doses, was completely inhibited by trimeth aphan. These findings are consistent with ANG II acting primarily on v ascular smooth muscle during acute infusion and via neural pathways du ring chronic treatment. The transition from direct smooth muscle to in direct neural action is rapid in rats (<10 h), and the MAP and neural responses to ANG II are dose related during chronic hypertension.