Endothelial potentiation of relaxation response to phentolamine in rat thoracic aorta.
In this study the role of the endothelium was evaluated in the relaxation of rat aortic rings induced by a number of alpha adrenergic antagonists. Phentolamine, a nonselective alpha adrenergic antagonist, relaxed rat aortic rings that were previously contracted with an EC80 dose of phenylephrine, in a concentration-dependent manner. Removal of the endothelium significantly reduced the sensitivity but not the amplitude of the response. The presence of endothelium also enhanced the vascular relaxation induced by yohimbine, a specific alpha-2 adrenergic antagonist (10(-8)-10(-6) M), and by prazosin, a specific alpha-1 adrenergic antagonist (10(-11)-10(-9) M). Both methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase, and eicosatetraynoic acid (3.2 X 10(-5) M) blocked the endothelial augmentation of vascular relaxation to phentolamine. Vessels precontracted with potassium chloride were slightly relaxed by phentolamine (10(-8)-10(-6) M) only with the endothelium was intact. Both methylene blue and eicosatetraynoic acid also inhibited the response to phentolamine in the intact vessels precontracted with potassium chloride. Prazosin (10(-9)-10(-7) M) and yohimbine (10(-8)-10(-6) M), unlike phentolamine, failed to induce relaxation in potassium chloride-precontracted vessels. When the vessels were precontracted with the thromboxane analog U46619 none of the three alpha antagonists induced vascular relaxation. These results indicate that the endothelium has a significant role in promoting relaxation induced by the three alpha adrenergic antagonists tested.
Mostaghim
R
R
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C.
Thomas
G
G
Ramwell
P W
PW
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D015117:5,8,11,14-Eicosatetraynoic Acid; D011189:Potassium Chloride; D008751:Methylene Blue; D010646:Phentolamine