Role of extrapulmonary conversion in mediating the systemic pressor activity of angiotensin I.
The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII. In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide. Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.
D000804:Angiotensin II / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A