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 mainly through sympathetic α₁-adrenergic effects of renal nerves supplying renal proximal tubules and renal vessels. Since previous studies on blockage of these nerves have been unequivocal due to confounding systemic effects and contralateral renal counterregulation, we administered doxazosin, an α₁-adrenoceptor antagonist, over 1 h into both renal arteries of four patients with decompensated cirrhosis. During the first 30 min of doxazosin infusion, when blood pressure was only slightly reduced, there was no evidence of improvement in sodium and water excretion. During the subsequent periods, blood pressure, renal plasma flow, glomerular filtration rate, and urinary output declined. The proximal tubular output of sodium, estimated on the lithium clearance, was initially unchanged, but decreased later during the infusion. Hyperreabsorption of sodium seemed to occur more markedly in the distal than in the proximal part of the nephron and was not alleviated by doxazosin. Urinary prostaglandin E₂ excretion was high but decreased in all patients after doxazosin. The study was terminated prematurely because the expected beneficial effects of doxazosin were clearly lacking, as renal function deteriorated temporarily in all the subjects studied. In conclusion, doxazosin given into the renal arteries of patients with decompensated cirrhosis did not improve the renal ability to excrete sodium. The results suggest that additional factors besides renal α₁-sympathetic activity play a major role in the renal sodium retention of patients with cirrhosis.