Effects of des-Asp-angiotensin I on experimentally-induced cardiac hypertrophy in rats.
We studied the effects of des-Asp-angiotensin I, a nine amino acid peptide, on cardiac hypertrophy caused by coarctation of the abdominal aorta in Sprague-Dawley rats. The nonapeptide was effective when given either intravenously or orally. Maximum attenuation was observed with an i.v. dose of 153 pmol/day for 4 days, and an oral dose of 250 nmol/day for 4 days. Three mg p.o. losartan, an angiotensin AT1 receptor antagonist, produced comparable attenuation. However, the attenuation produced by des-Asp-angiotensin I but not by losartan was blunted by 30.4 micromol of indomethacin. The oral efficacy of the nonapeptide was partly due to its low effective i.v. doses which were in the nM range. This range is below the Km of most enzymes including those of the intestinal peptidases (the Km of most enzymes is in the microM range). However, the mechanism of absorption of the peptide from the GIT into the systemic circulation remains to be investigated. The findings demonstrate for the first time, the anti-cardiac hypertrophic action of an angiotensin peptide. Unlike the ACE inhibitors and angiotensin receptor antagonists, the nonapeptide acts as an agonist on an indomethacin-sensitive angiotensin receptor to exert its action.
Sim
M K
MK
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore.
Min
L
L
D000803:Angiotensin I / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000819:agonists* / Q000187:drug effects
D011945:Receptors, Angiotensin; D000803:Angiotensin I; D007213:Indomethacin