DOXAZOSIN GIVEN INTO THE RENAL-ARTERIES OF PATIENTS WITH CIRRHOSIS - EFFECTS ON RENAL SODIUM HANDLING, HEMODYNAMICS AND HORMONES

Excessive sodium retention in cirrhosis is believed to be mediated mai nly through sympathetic alpha(1)-adrenergic effects of renal nerves su pplying renal proximal tubules and renal vessels. Since previous studi es on blockage of these nerves have been unequivocal due to confoundin g systemic effects and contralateral renal counterregulation, we admin istered doxazosin, an alpha(1)-adrenoceptor antagonist, over 1 h into both renal arteries of four patients with decompensated cirrhosis. Dur ing the first 30 min of doxazosin infusion, when blood pressure was on ly slightly reduced, there was no evidence of improvement in sodium an d water excretion. During the subsequent periods, blood pressure, rena l plasma flow, glomerular filtration rate, and urinary output declined . The proximal tubular output of sodium, estimated on the lithium clea rance, was initially unchanged, but decreased later during the infusio n. Hyperreabsorption of sodium seemed to occur more markedly in the di stal than in the proximal part of the nephron and was not alleviated b y doxazosin. Urinary prostaglandin E(2) excretion was high but decreas ed in all patients after doxazosin. The study was terminated premature ly because the expected beneficial effects of doxazosin were clearly l acking, as renal function deteriorated temporarily in all the subjects studied. In conclusion, doxazosin given into the renal arteries of pa tients with decompensated cirrhosis did not improve the renal ability to excrete sodium. The results suggest that additional factors besides renal alpha(1)-sympathetic activity play a major role in the renal so dium retention of patients with cirrhosis. (C) 1997 Elsevier Science I reland Ltd.