GLUCOSE IN CONJUNCTION WITH PEPTIDES DERI VED FROM KININOGENS MIGHT ACT FROM DIGESTIVE-TRACT AS BLOCKERS OF ANP MEDIATED DIURESIS-NATRIURESIS

This paper describes long term research effort which have lead 1) to t he identification of peptides present in pepsanurin, a peptidic fracti on obtained by pepsin hydrolisis of plasma globulins that inhibits the renal excretory action of atrial natriuretic peptide (ANP) and 2) to the discovery of an unexpected role of glucose, as a requisite for the se inhibitory effects. The active peptides identified in pepsanurin ar e derived from plasma kininogens, substrates of the kallikrein-kinin s ystem. Pro-kinins of 15, 16 and 18 aminoacids, and bradkinin itself, b lock ANP-induced diuresis and natriuresis when injected iv ip or into the duodenal lumen of anesthetized rats in picomol doses. Furthermore, an novel 20 aminoacids fragment derived from kininogen dominium-1, na med PU-D1, is the most potent and longer lasting blocker of ANP renal effects. The anti-ANP effects of those peptides are prevented by B2-ki nin receptor antagonists. The inhibition of ANP by kinins and PU-D1 wa s evident only in rats infused with isotonic glucose; whereas the excr etory effect of ANP was not effected in fasted rats not infused, or in fused with saline. These findings provide evidence that glucose facili tates liquid retention through a kinin-mediated inhibition of ANP excr etory action that may be related to the prandial cycle.