ROLE OF PROSTAGLANDINS AND RENAL NERVES IN THE RENAL ACTIONS OF ADRENOMEDULLIN

Adrenomedullin (ADM), originally discovered in human pheochromocytoma, is also of renal cell origin and has natriuretic and diuretic actions . The present study was designed to investigate the role of prostaglan dins and renal nerves in the renal hemodynamic and natriuretic actions of ADM. ADM was administered intrarenally (1, 5 and 25 ng . kg(-1). m in(-1)) with and without prostaglandin inhibition (meclofenamate, 5 mg /kg intravenous bolus) in anesthetized normal mongrel dogs (n = 5, eac h). To elucidate the role of renal nerves, ADM was administered intrar enally to the denervated kidney in five dogs. ADM mediated a natriuret ic action via increases in glomerular filtration rate and decreases in distal tubular sodium reabsorption, which was attenuated by renal den ervation and completely abolished by prostaglandin inhibition. The ren al vasodilatation induced by ADM was attenuated by meclofenamate, as w ell as by renal denervation, although not significantly. Additionally, renal nerves mediated hemodynamic effects of hypertension that were p roduced by intrarenal infusion of ADM. This study establishes an impor tant mechanistic role for renal prostaglandins as a mediator of ADM-me diated natriuresis at the level of the glomerulus and terminal nephron .