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 micrograms X kg-1 X 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 decreased 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 intravertebral saralasin did not differ from the increase produced by intravenous 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 micrograms/dl, P less than 0.05) by intravenous infusion of the highest dose of saralasin, but neither intracarotid nor intravertebral saralasin infusion altered plasma corticosteroid concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000305:Adrenal Cortex Hormones / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003243:Consciousness / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000008:administration & dosage / Q000494:pharmacology; D012964:Sodium / Q000172:deficiency*
D000305:Adrenal Cortex Hormones; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012964:Sodium; D012083:Renin; D012504:Saralasin