A y-Melanocyte Stimulating Hormone-like Peptide Causes Reflex Natriuresis After Acute Unilateral Nephrectomy

Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-/3-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that -y-melanocyte stimulating hormone (yMSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive y-MSH-like material was 40 ± 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive y-MSH was 81 ± 36 fmol/ml (p<0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive y-MSH (r= 0.75, p< 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against y-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic y-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-y-MSH antiserum blocked this effect of peptide infusion. In a final group of rats, synthetic y-MSH infused directly into one renal artery at a rate of 300 fmol/min caused a prompt increase in UNaV from the infused kidney but not the contralateral kidney. These studies thus indicate that plasma immunoreactive y-MSH activity is increased after acute unilateral nephrectomy in a manner related to the magnitude of the postnephrectomy natriuresis, that the natriuresis is not observed in rats exposed to antibodies to yMSH, and that y-MSH itself possesses natriuretic properties through a direct renal action. y-MSH or a related peptide therefore appears to be a critical element in the response to unilateral nephrectomy, functioning as a natriuretic hormone to stimulate the postnephrectomy natriuresis. (Hypertension 10: 619-627, 1987)