Characterization of intrarenal arterial adrenergic receptors in renovascular hypertension.
alpha-Adrenergic receptor subtypes were investigated using [3H]prazosin, an alpha 1 selective antagonist, and the alpha 2 selective antagonist [3H]rauwolscine in a smooth muscle plasma membrane enriched microsomal fraction prepared from rabbit intrarenal arterial vasculature. Both radioligands displayed single components on Scatchard analysis. The specific binding of [3H]prazosin was of high affinity (0.54 +/- 0.04 nM) with a maximum binding capacity (Bmax) of 212 +/- 15 fmol/mg protein. The maximum number of [3H]rauwolscine binding sites was 64 +/- 4 fmol/mg of protein with a dissociation constant (Kd) of 5.60 +2- 0.27 nM. Binding of both radioligands was rapid, saturable, and specific. alpha 1- and alpha 2-adrenergic receptors in the intrarenal arterial membrane preparation were also characterized at 2-, 4-6-, and 10-12-week intervals during the course of development and maintenance of chronic two-kidney, one clip (2K1C) Goldblatt hypertension and in age-matched sham-operated normotensive control rabbits. The alpha 1-adrenergic receptor affinity for [3H]prazosin binding in hypertensive rabbits was significantly increased in the stenotic, but not contralateral, kidney at 2 weeks; however, at 6 weeks the receptor affinity of both kidneys was significantly increased compared with those of the normotensive control group. No difference in alpha 1-adrenergic receptor affinity was seen at 12 weeks, and there were no changes in Bmax at any of the weekly intervals. Neither the Kd, nor Bmax, for [3H]rauwolscine in either kidney showed a significant difference between hypertensive rabbits and normotensive control rabbits. These studies demonstrate the existence in the rabbit intrarenal arterial vasculature of binding sites with alpha 1- and alpha 2-adrenergic receptor specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
McElroy
N D
ND
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455.
Zimmerman
B G
BG
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012077:Renal Artery / Q000294:innervation*; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin