Effects of blockade of brain angiotensin II receptors in conscious, sodium-deprived dogs

The present studies were designed to evaluate the physiological significance of the actions of angiotensin II (ANG II) on the brain. The effects of blockade of brain ANG II receptors by intracarotid or intravertebral infusions of saralasin were studied in conscious dogs with high circulating ANG II levels (142 ± 16 pg/ml) due to a low-sodium diet. Three doses of saralasin were infused into each pair of arteries and intravenously: 0.1, 0.3, and 1.0 μg.kg^-1.min^-1. Saralasin produced dose-related decreases in arterial pressure during infusion into the carotid or vertebral arteries, confirming that ANG II maintains arterial pressure during sodium deficiency. However, intravenous saralasin administration decreases pressure to a similar degree, suggesting that the hypotensive effect was due to recirculation of saralasin, rather than to blockade of a central action of circulating ANG II. Heart rate was not altered by infusion of saralasin by any route. Saralasin administration also caused a dose-dependent increase in plasma renin activity and plasma ANG II concentration. However, because the increases produced by intracarotid or saralasin did not differ from the increase produced by intravenous intravertebral infusion, these results do not provide evidence that renin release is modulated by a central action of ANG II during sodium deficiency. Plasma corticosteroid levels were reduced (2.4 ± 0.5 to 1.4 ± 0.2 μg/dl, P < 0.05) by intravenous infusion of the highest dose of saralasin, but neither intracarotid nor intravertebral saralasin infusion altered plasma corticosteroid concentration. It therefore appears that during sodium deficiency, ANG II exerts a stimulatory effect on corticosteroid secretion by a direct adrenal action rather than by increasing adrenocorticotropin (ACTH) secretion. These results confirm that the renin-angiotensin system plays an important role in the control of blood pressure, renin secretion, and corticosteroid secretion during sodium deficiency but do not provide evidence that the control is mediated via actions of ANG II on the brain.