Blockade of the response to volume expansion by monoclonal antibodies against atrial natriuretic peptides.
It is known that plasma levels of atrial natriuretic peptides (ANP) increase in response to volume expansion. However, the extent to which these increased levels of ANP participate in the renal response to volume expansion remained unknown. This question can be answered with the aid of a monoclonal antibody that binds specifically to the biologically active forms of ANP: Ascitic fluid containing this monoclonal antibody dose-dependently and specifically blocks the natriuretic, diuretic and hypotensive effects of synthetic atriopeptin II given intravenously in rats. Volume expansion induced by injection of 20 ml/kg homologous blood in anaesthetized rats evokes massive diuresis and natriuresis. Pretreatment with ascitic fluid containing monoclonal antibody completely blocks this diuretic and natriuretic response during the first 20 min after volume expansion. Thus the initial renal response to volume expansion is due to the increase in endogenous ANP. Similar results were obtained for volume expansion with isotonic saline in conscious rats. It is supposed that the effects of ANP are mediated through particulate guanylate cyclase activation and intracellular cyclic guanosine-monophosphate (cGMP) accumulation in target tissues including renal and vascular smooth muscles cells. Besides increasing plasma ANP levels (measured by radioimmunoassay) volume expansion also induces an increase of cGMP levels both in plasma, urine and in renal tissue. This increase is ANP-dependent as it can be blocked by the monoclonal antibody.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D001769:Blood; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor