Augmentation of the natriuretic activity of exogenous and endogenous atriopeptin in rats by inhibition of guanosine 3',5'-cyclic monophosphate degradation.
To investigate the relationship between AP, cyclic GMP, and sodium excretion, we studied the effect of a cyclic GMP phosphodiesterase inhibitor (M + B22948) on the natriuretic response to (a) an infusion of AP (103-126) and (b) acute volume expansion in rats. The phosphodiesterase inhibitor markedly potentiated the effect of low-dose AP infusions on urinary sodium and cyclic GMP excretion without potentiating the fall in blood pressure. Acute volume expansion (1% body wt) led to small but significant (P less than 0.01) rises in plasma AP and urinary cyclic GMP levels. Pretreatment with the phosphodiesterase inhibitor enhanced the natriuretic and cyclic GMP response to volume loading, an effect that was attenuated by administration of a monoclonal antibody directed against AP. These data indicate that cyclic GMP mediates the natriuretic activity of AP and AP and cyclic GMP play active roles in the natriuresis of acute volume expansion. Moreover, pharmacological manipulation of cyclic GMP levels may prove a useful therapeutic strategy for facilitating the natriuretic but not the hypotensive effects of AP.
Wilkins
M R
MR
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Settle
S L
SL
Needleman
P
P
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D009320:Atrial Natriuretic Factor / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D011688:Purinones; D009320:Atrial Natriuretic Factor; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP