Characterization of bunazosin-sensitive alpha1-adrenoceptors in human renal medulla

J Cardiovasc Pharmacol. 1997 Aug;30(2):163-8. doi: 10.1097/00005344-199708000-00003.

Abstract

We studied the characteristics of bunazosin-sensitive alpha1-adrenoceptors in human renal medullae by using renal-clearance studies and radioligand-binding assay. In 12 patients with hypertension, renal-clearance 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 +/- 0.02 mm Hg/(ml/min) (p < 0.05), but that prazosin had little effect on renal function. In a radioligand-binding assay, specific, saturable, and stereoselective [3H]bunazosin binding, with a single class of binding sites (Kd = 2.7 +/- 1.4 nM; Bmax = 44 +/- 16 fmol/mg protein; n = 11) was detected in membrane preparations of human renal medullae. The rank order of potency of antagonists that inhibited [3H]bunazosin-binding was bunazosin (Ki in nM = 49) > prazosin (57) > yohimbine (3,900) > propranolol (29,000), and that of agonists, l-norepinephrine (7,400) > l-epinephrine (19,000) > d-norepinephrine (71,000). The competition curves fit a one-site model. These findings suggest that bunazosin-sensitive alpha1-adrenoceptors exist in human renal medullae and participate in the regulation of renal hemodynamics.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists / pharmacokinetics
  • Adrenergic alpha-Antagonists / pharmacology*
  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • In Vitro Techniques
  • Kidney Function Tests
  • Kidney Medulla / drug effects
  • Kidney Medulla / metabolism*
  • Male
  • Middle Aged
  • Prazosin / pharmacokinetics
  • Prazosin / pharmacology
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology*
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-1 / metabolism*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Quinazolines
  • Receptors, Adrenergic, alpha-1
  • bunazosin
  • Prazosin