CHARACTERIZATION OF BUNAZOSIN-SENSITIVE ALPHA(1)-ADRENOCEPTORS IN HUMAN RENAL MEDULLA

We studied the characteristics of bunazosin-sensitive alpha(1)-adrenoc eptors in human renal medullae by using renal-clearance studies and ra dioligand-binding assay. In 12 patients with hypertension, renal-clear ance studies demonstrated that bunazosin significantly increased renal blood flow from 683 +/- 82 (SD) to 829 +/- 103 ml/min (p < 0.05) and decreased renal vascular resistance from 0.18 +/- 0.02 to 0.14 +/- 0.0 2 mm Hg/(ml/min) (p < 0.05), but that prazosin had little effect on re nal function. In a radioligand-binding assay, specific, saturable, and stereoselective [H-3]bunazosin binding, with a single class of bindin g sites (K-d = 2.7 +/- 1.4 nM; B-max = 44 +/- 16 fmol/mg protein; n = 11) was detected in membrane prepara tions of human renal medullae. Th e rank order of potency of antagonists that inhibited [H-3]bunazosin-b inding was bunazosin (K-i in rM = 49) > prazosin (57) > yohimbine (3,9 00) > propranolol (29,000), and that of agonists, I-norepinephrine (7, 400) > I-epinephrine (19,000) > d-norepinephrine (71,000). The competi tion curves fit a one-site model. These findings suggest that bunazosi n-sensitive alpha(1)-adrenoceptors exist in human renal medullae and p articipate in the regulation of renal hemodynamics.