Evidence for bradykinin potentiation by angiotensin congeners in conscious rats.
It has become increasingly clear that the potent vasoactive peptides bradykinin and angiotensin share a common point of metabolism, i.e., angiotensin-converting enzyme or kininase II, and may interact with prostaglandins to regulate regional blood flow. To establish whether the sensitivity to exogenous bradykinin was affected by the presence of angiotensin, vasodepressor dose-response curves to injected bradykinin were performed in conscious rats before and during a 1-h infusion of angiotensin I (30 ng/min), angiotensin II (30  and 300 mg/min), and [Sar2,Ala8]angiotensin II (5 micrograms/min). All of these induced a parallel leftward shift of the bradykinin dose-response curve of approximately threefold. No similar changes were observed during control infusions of dextrose, similar pressor doses of lysine vasopressin, or norepinephrine. Sensitivity to bradykinin was enhanced by saralasin in normal and nephrectomized rats, suggesting that the antagonist itself was responsible. Similar potentiation was present during both acute (1 h) and chronic infusions (9 days) of angiotensin II and attenuated the effect of a converting-enzyme inhibitor on bradykinin sensitivity. Accordingly, these results suggest a competitive interaction in vivo between angiotensin congeners and bradykinin at a point of bradykinin degradation, probably angiotensin-converting enzyme or kininase II. This is a potential additional mechanism by which these systems may interact to affect regional blood flow and must be considered in the interpretation of results obtained during saralasin infusion.
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007263:Infusions, Parenteral; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000809:Angiotensins; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012504:Saralasin; D001920:Bradykinin