Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response.
Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000311:Adrenal Glands / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004285:Dogs; D006854:Hydrocortisone / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface; D012083:Renin / Q000378:metabolism; D012965:Sodium Chloride
D010455:Peptides; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone; D003907:Dexamethasone; D012083:Renin; D003345:Corticosterone; D006854:Hydrocortisone