Changes in alpha 2-adrenoceptors on vascular smooth muscle and neural membranes following hypertension induced by renal ischemia.
alpha 2-Adrenoceptors were characterized on neural and vascular membranes from 2-kidney-1-clip renal hypertensive (RHT) and normotensive (NT) rats. Rats were sacrificed 6 weeks after induction of renal ischemia, and the specific binding of 3H-clonidine to smooth muscle membranes form tail arteries and neural membranes from various brain regions was examined. Additionally, isometric contractions of helically cut tail artery strips produced by various alpha-adrenoceptor agonists were measured. Scatchard analysis indicated an increased number of high-affinity binding sites on the smooth muscle membranes from RHT rats (Bmax = 43.5 +/- 1.4 fmol/mg protein) compared to that from the NT rats (25.4 +/- 3.8 fmol/mg protein). An increased contractile sensitivity to clonidine was also observed in tail artery strips from RHT rats (EC50 for RHT = 3.04 x 10(-8) M; NT = 1.52 x 10(-7) M). In neural tissue, the number of alpha 2-adrenoceptor-binding sites was significantly increased in the locus coeruleus from RHT rats, but not in the amygdala, hypothalamus, parietal cortex, hippocampus or lower brain stem. These results demonstrate that renal ischemia produces changes in both peripheral and neural alpha 2-adrenoceptor density. The increase in smooth muscle alpha 2-adrenoceptors might also provide a partial explanation for the supersensitivity to adrenergic agonists in this model of hypertension.
Department of Pharmacology, University of Michigan, Ann Arbor.
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RE
Weishaar
R C
RC
Webb
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CB
Smith
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D013623:Tail / Q000098:blood supply
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha