A FRAGMENT OF HUMAN KININOGEN CONTAINING BRADYKININ BLUNTS THE DIURETIC EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE

A synthetic 15 amioacids kinin, named PU-15, is able to block the diur etic natriuretic action of Atrial Natriuretic Peptide (ANP), The struc ture of PU-15 is Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg having th e aminoacid sequence of a fragment of human kininogens, The increase I n the urinary excretion of sodium, potassium, and water, elicited by a bolus of 0.5 mu g of ANP in anesthetized rats, is blocked by PU-15 (1 00-150 ng) given either intravenously 3 min before ANP injection, or i njected intraperitoneally or in the duodenal lumen, 40 min before ANP, This ANP blockade, which mimics the action of pepsanurin, is only obt ained with doses of PU-15 in a narrow range around 100 picomol/rat, an d do not modify blood pressure, Larger doses, 2- to 8-fold the effecti ve dose, either do not change the response to ANP or raise the excreti on of sodium and water, The administration of HOE-140, a bradykinin B2 receptor blocker, prior to PU-15, completely abolishes the anti-ANP a ction of PU-15, These findings lend support to the proposal that kinin s released from the intestinal tract during prandial period can modula te renal excretory function.