RENAL LOCALIZATION AND ACTIONS OF ADRENOMEDULLIN - A NATRIURETIC PEPTIDE

Adrenomedullin (ADM) is a newly described 52-amino acid peptide origin ally isolated from extracts of human pheochromocytoma and, more recent ly, detected in human plasma. Based on the report that ADM mRNA and im munoreactivity are present in the kidney, the current study was design ed to determine the renal distribution of ADM by immunohistochemistry and the renal biological actions of ADM. In the immuno-histochemical s tudies, the present investigation demonstrated the localization of ADM in glomeruli, cortical distal tubules, and medullary collecting duct cells of the normal canine kidney. In the in vivo studies, ADM was adm inistered (0.25 ng . kg(-1). min(-1) in group I and 1, 5, and 25 ng . kg(-1). min(-1) in group II) intrarenally in normal mongrel dogs with the contralateral kidney receiving only saline vehicle. Intrarenal inf usion of ADM resulted in a marked diuretic and natriuretic response, w hereas the contralateral kidney showed no renal effects. These signifi cant natriuresis and diuresis in the ADM kidney were associated with i ncreases in glomerular filtration rate and fractional sodium excretion and with a decrease in distal tubular sodium reabsorption. Intrarenal infusion of ADM also caused an increase in mean arterial blood pressu re and a decrease in heart rate. Plasma concentrations of atrial natri uretic peptide, renin activity, aldosterone, and guanosine 3',5'-cycli c monophosphate were not changed during the infusion of ADM. The curre nt study demonstrates that ADM is present in renal glomerular and tubu lar cells and is a potent natriuretic peptide that may play an importa nt role in the regulation of sodium excretion.