Studies were performed to examine whether atrial natriuretic peptide (ANP) has a direct action on glomerular afferent arterioles, and if so, whether the action is mediated by guanosine 5'-cyclic monophosphate (cGMP). A single superficial afferent arteriole was dissected from the canine kidney and perfused with the single glomerular perfusion technique described by Osgood et al. [Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F349–F354, 1983]. Norepinephrine (NE, 1 x 10(-6) M) significantly increased arteriolar resistance, calculated from the perfusion rate and arteriolar pressure. Synthetic human ANP (hANP) provoked afferent arteriolar dilation and attenuated the NE-induced increase in arteriolar resistance with 1 x 10(-10) to 1 x 10(-6) M concentrations. This vasodilatory effect was significantly potentiated by 2-o-propoxyphenyl-8-azapurin-6-one (M&B 22,948, 4 x 10(-12) M), a cGMP phosphodiesterase inhibitor, probably due to a sequential interaction of synergistic drugs. Also, the 1 x 10(-4) M concentration of 8-bromoguanosine 5'-cyclic monophosphate or dibutyryl guanosine, 5'-cyclic monophosphate (DBcGMP) lessened NE-induced arteriolar constriction, but DBcAMP did not. We conclude from these observations that ANP has a direct vasodilatory action on canine glomerular afferent arterioles, and that this ANP-induced vasodilation is mediated by enhanced cGMP synthesis.
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