Pressor and stereoidogenic actions of [des-Asp1]angiotensin I dependency on conversion to angiotensin III.
In the conscious rat, angiotensin III, [des-Asp1]angiotensin II, stimulates aldosterone biosynthesis and exhibits 30-50% of the pressor potency of angiotensin II. A potential precursor of the biologically active heptapeptide is [des-Asp1]angiotensin I, the C-terminal nonapeptide of angiotensin I. The in vivo pressor and the in vivo and in vitro steroidogenic actions of [des-Asp1]angiotensin I were investigated in the presence and absence of an inhibitor of converting enzyme. The pressor responses to [des-Asp1]angiotensin I and [des-Asp1]angiotensin II were similar and showed comparable changes in responsiveness when the rats were maintained on diets with different sodium content. The pressor activity of [des-Asp1]angiotensin I was attenuated progressively by pretreatment with increasing doses of converting enzyme inhibitor and was totally abolished in five of seven rats at an inhibitor dose of 1,200 microng/kg. In isolated zona glomerulosa cells from rats on normal sodium diets, angiotensin I and [des-Asp1]angiotensin I had only weak steroidogenic effects relative to angiotensin III. The administration of [des-Asp1]angiotensin I, 1 nmol/kg, subcutaneously to six rats on normal sodium diets resulted in a rise in the 6-hour urinary aldosterone excretion from 46.5 +/- 6.6 to 99.5 +/- 11.8 ng (P less than 0.01). Treatment with converting enzyme inhibitor (2 mg/kg) prevented this steroidogenic response to [des-Asp1]angiotensin I. These in vivo studies in the conscious rat show that the administration of [des-Asp1]angiotensin I results in increases in both blood pressure and urinary aldosterone excretion which are dependent on the hydrolysis of the nonapeptide by converting enzymes to angiotensin III. If [des-Asp1]angiotensin I is formed in this species, then it will be an immediate precursor of angiotensin III.
D000302:Adrenal Cortex / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis* / Q000652:urine; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D012964:Sodium / Q000008:administration & dosage
D000804:Angiotensin II; D000805:Angiotensin III; D000450:Aldosterone; D012964:Sodium