Decreased potency of contraction to alpha-adrenoceptor stimulation in renal arteries from obese hypertensive dogs.
The contractile potencies of the alpha-adrenoceptor agonist phenylephrine (PhE) and two nonadrenergic vasoconstrictors, prostaglandin F2 alpha (PGF2 alpha) and endothelin, were evaluated in renal arterial muscle strips isolated from obese hypertensive (OH) dogs. Responses were compared with those obtained from renal arteries isolated from lean normotensive (LN) dogs. Identical dose-response curves were produced by PGF2 alpha in arteries from OH and LN dogs. This was also true for endothelin. However, the vasoconstrictor potency of PhE for arteries from OH dogs was approximately 2.5-fold less than that for arteries from LN dogs. This difference was not dependent on endothelial integrity. Although they were less potent to PhE, arteries from OH dogs did not produce weaker maximum contractile responses than arteries from LN dogs; responses produced by maximum K+ depolarization (S(o)) were approximately 2 x 10(5) N/m2, and responses to the maximally effective concentrations of PhE, PGF2 alpha, and endothelin were approximately 0.97-, 0.50-, and 0.87-fold S(o), respectively. In addition to the rightward shift in contractile potency to PhE, arteries from OH dogs precontracted with a maximum PhE concentration relaxed more to a high nitroglycerin concentration than did arteries from LN dogs. At a PhE concentration that produced equivalent maximum force responses, arteries from OH dogs had a lower rate of muscle shortening than did arteries from LN dogs, suggesting reduced cross-bridge activation in the arteries from OH dogs. These data suggest that alpha-adrenoceptor-induced activation was selectively downregulated in renal arteries from OH dogs.
Ratz
P H
PH
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
West
D B
DB
Granger
J P
JP
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D005996:Nitroglycerin / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000294:innervation*; D014661:Vasoconstriction; D014664:Vasodilation
D016232:Endothelins; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015237:Dinoprost; D005996:Nitroglycerin