Cardiovascular adrenoreceptor number and function in experimental hypertension in the baboon.
We studied adrenoreceptor density and affinity in the myocardial and pooled arterial smooth muscle membranes in a baboon model (Grollman 2-kidney, 2-figure-of-8) of hypertension, using tritiated prazosin (alpha 1-antagonist), yohimbine (alpha 2-antagonist) and dihydroalprenolol (beta-antagonist) as ligands. By the end of 24 weeks, mean arterial blood pressure had increased from 105 +/- 3 to 155 +/- 8 mm Hg, and heart rate increased from 102 +/- 6 to 118 +/- 2/min. In the myocardium, there was a significant decrease in alpha 2- and beta-receptor density, and significant decreases in alpha 1-, alpha 2- and beta-receptor KD values. In membranes from arteries, Bmax for alpha 1- and alpha 2-receptors more than doubled, with significantly increased Kd values for both receptor subtypes. The decrease in myocardial beta-receptor density may represent a down-regulatory response to the increased sympathetic activity in this type of hypertension, and the decreased Bmax for myocardial alpha 2-receptors may cause a decreased feedback inhibition of norepinephrine release from sympathetic nerve terminals, contributing to the increased heart rate. The increase in both alpha-receptor subtypes in arteries may be part of the pathogenesis of the hypertension. However, we were unable to show increased chronotropic responses to infused isoproterenol, or increased blood pressure responses to phenylephrine.
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Hurwitz
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Rosendorff
D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010215:Papio; D010656:Phenylephrine / Q000494:pharmacology; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D007545:Isoproterenol