Localization of cGMP after infusion of ANP or nitroprusside in the maturing rat

Abstract

To determine the ontogeny of intrarenal distribution of guanosine 3',5'-cyclic monophosphate (cGMP) formation in response to atrial natriuretic peptide (ANP) or sodium nitroprusside (SNP), adult and neonatal Sprague-Dawley rats were anesthetized and infused for 60 s with rat ANP (5-2,500 micrograms/kg) or SNP (0.1-10.0 mg/kg). cGMP was identified by the immunoperoxidase technique using a specific antibody. In adult rats, infusion of ANP localized cGMP primarily to the glomerular podocytes, whereas stimulation by SNP increased cGMP in the mesangium only (P less than 0.01). In neonatal rats, although overall renal cGMP immunostaining was greater than in adults, specific localization to podocytes (ANP) or mesangium (SNP) resulted only with higher doses of agonists. Although basal generation of cGMP by isolated glomeruli was greater in neonatal rats, the threshold for stimulation by ANP was lower in glomeruli from adult rats. We conclude that in vivo ANP stimulates glomerular particulate guanylate cyclase primarily in the podocytes, whereas SNP stimulates soluble guanylate cyclase localized to the mesangial cells. There is a maturational increase in the sensitivity for activation of glomerular particulate and soluble guanylate cyclase.