MECHANISM OF THE NATRIURETIC ACTION OF GAMMA-MELANOCYTE-STIMULATING HORMONE

To explore the mechanism underlying the natriuretic effect of gamma-me lanocyte-stimulating hormone (gamma-MSH), we infused the peptide intra venously at 200 pmol/min into anesthetized rats. gamma-MSH led to a pr ogressive increase in urinary sodium excretion (UNaV), whereas continu ous infusion of the vehicle did not affect UNaV. Plasma immunoreactive gamma-MSH was nine times greater at 120 min after the start of the in fusion than in vehicle-infused rats. Plasma atrial natriuretic peptide (ANP) concentration also increased as a consequence of the gamma-MSH infusion, and a strong correlation existed between the concentrations of the two peptides (n = 17, r = 0.81, P < 0.001). Urinary excretion o f guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic mono phosphate increased as a result of the infusion. Antiserum to rat ANP blunted the natriuresis only slightly, suggesting that the increase in plasma ANP concentration was not a critical element in gamma-MSH natr iuresis. gamma-MSH had no effect on ANP release from isolated rat righ t atrial strips superfused in vitro. Infusion of gamma-MSH (500 fmol/m in) directly into one renal artery led to an ipsilateral natriuresis w ithout change in UNaV from the contralateral kidney. Prior denervation of the infused kidney prevented the natriuresis resulting from intrar enal infusion. Intrarenal infusion of ANP (800 fmol/min) also produced ipsilateral natriuresis, which, however, was not affected by renal de nervation. These studies confirm that the natriuretic action of gamma- MSH occurs primarily by an interaction with the renal nerves. Intraven ous infusion of the peptide sufficient to produce a supraphysiological plasma gamma-MSH concentration also results in an increase in plasma ANP concentration; however, this increase at best plays only a minor r ole in the natriuresis following intravenous gamma-MSH infusion.