(Des-Asp1) angiotensin I: a study of its pressor and steroidogenic activities in conscious rats.
The steroidogenic and pressor activities of the nonapeptide (des-Asp1) angiotensin I [(des-Asp)-AI] were tested in conscious rats. (des-Asp)-AI caused dose related increases in mean arterial pressure (MAP), serum aldosterone, and serum corticosterone in doses between 3 and 3,000 ng/kg/min. (des-Asp)-AI was 14% as potent as angiotensin I and angiotensin II and 60% as potent as (des-Asp1) angiotensin II [des-Asp)-AII] in raising MAP. (des-Asp)-AI was less active than AI, AII, or (des-Asp)-AII in causing increased release of aldosterone, possessing only 8%, 11%, and 17% of the potency of AII, (des-Asp)-AII, and AI, respectively. Each of these angiotensin peptides was equally potent in elevating serum corticosterone levels. Infusions of a nonapeptide inhibitor of converting enzyme (CEI, 0.5 mg/kg/min iv) did not alter control MAP or blood pressure responses to AII or (des-Asp-)-AII but inhibited equally the blood pressure effects of AI and (des-Asp)-AI. CEI also inhibited the ability of (des-Asp)-AI (67% inhibition) and AI (34% inhibition) to increase the serum aldosterone concentration, but had no effect on basal aldosterone levels. These data indicate that (des-Asp)-AI has pressor and steroidogenic effects, but requires conversion to (des-Asp)-AII for a major portion of its activity. These results further substantiate the hypothesis that (des-Asp)-AII, recently recognized as a hormone of the renin-angiotensin system, may be produced without the formation of AII as an intermediate and provide in vivo evidence for the conversion of (des-Asp)-AI to (des-Asp)-AII.
D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000805:Angiotensin III; D000450:Aldosterone; D003345:Corticosterone