Selective inhibition by des-1-Asp-8-lle-angiotensin ii of the steroidogenic response to restricted sodium intake in the rat.
Angiotensin III (des-1-Asp-angiotensin II) is a potent steriodogenic agent in many species. The effects of the heptapeptide in the adrenal zona glomerulosa are resistant to blockade by C-terminally substituted analogues of angiotensin II (1-Sar-8-Ile- or 1-Sar-8-Ala-octapeptides). For this reason, the effects of 7-Ile-angiotensin III, a C-terminally substituted analogue of the heptapeptide, and 1-Sar-8-Ile-angiotensin II on aldosterone biosynthesis in rabbit adrenal cortical cell suspensions and on urinary aldosterone excretion in sodium-deprived rats were studied. In the vitro studies, 7-Ile-angiotensin III was a better antagonist of angiotensin II- or angiotensin III-induced steroidogenesis than was 1-Sar-8-Ile-angiotensin II. In the rats, subcutaneously administered 1-Sar-8-Ile-angiotensin II (0.9 mumoles/kg) produced prolonged blockade of the pressor responses to exogenous angiotensin II. 70Ile-angiotensin III (0.9 mumoles/kg) had no effect on resting blood pressure or on blood pressure responses to angiotensin II infusions. At the doses studied, however, 7-Ile-angiotensin III caused a marked decrease (50%) in aldosterone excretion in sodium-deprived rats, but 1-Sar-8-Ile-angiotensin II had no effect on aldosterone excretion. In the sodium-deprived rats, the administration of 7-Ile-angiotensin Ile was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity, but otensin III was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity. These results are consistent with a role for angiotensin III in the control of aldosterone biosynthesis.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis* / Q000652:urine; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000652:urine; D011817:Rabbits; D051381:Rats; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000172:deficiency* / Q000652:urine
D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D011188:Potassium