Abstract
The role of the brain renin-angiotensin system (RAS) in pressor responses to norepinephrine (NE) and angiotensin II (AII) and in baroreflex sensitivity was examined in two-kidney, one-clip rats with renal artery stenosis of 2 days' duration (2K1C) and sham-operated controls by intraventricular and intravenous administration of an AII antagonist, [1-Sar, 8-Ala] angiotensin II (saralasin).
In 2K1C rats, mean arterial pressure (MAP) was increased as compared with controls and an exaggerated pressor response to NE was observed. The intraventricular infusion of saralasin (0.5 μg/kg/min for 30 min), which did not change MAP in either group of rats, abolished the hyperresponse in 2K1C rats. After obtaining the pressor response to NE, the same dose of saralasin used intraventricularly was infused intravenously for 30 min. The MAP in 2K1C rats was decreased, but that in controls was not changed ; the pressor response to NE was not altered in either of the two groups. Baroreflex sensitivity was decreased in 2K1C rats. The intraventricular infusion of saralasin restored the decreased baroreflex sensitivity in 2K1C rats. Plasma renin activity (PRA) was elevated in 2K1C rats as compared with controls. Plasma NE concentrations were not different in the two groups and they were not altered by the intraventricular infusion of saralasin. The intraventricular infusion of saralasin decreased PRA in 2K1C rats, whereas it increased PRA in controls. The pressor response to AII in the two groups was inversely related to the level of PRA, both before and during the intraventricular infusion of saralasin.
These results suggest that 1) the brain RAS is involved in the enhanced pressor response to NE in 2K1C rats, but not in the response to AII ; 2) the exaggerated response to NE is not mediated through either the peripheral RAS or the plasma NE levels, but induced in part by decreased baroreflex sensitivity, and 3) the brain RAS may have a role in modulating the peripheral PRA.
