Alpha adrenoceptor subtypes and receptor reserve in human versus canine saphenous vein: sensitivity to blockade by nitroglycerin
Eskinder, H.; Hillard, C.J.; Olinger, G.N.; Christensen, C.W.; Baker, J.E.; Warltier, D.C.; Gross, G.J.
Journal of Pharmacology and Experimental Therapeutics 247(3): 941-948
1988
ISSN/ISBN: 0022-3565 PMID: 2905005 Document Number: 310727
The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10-7 M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree. However, the alpha-1-mediated response of phenylephrine in human saphenous vein was more sensitive to nitroglycerin that the phenylephrine-induced contraction in canine saphenous vein. These results demonstrate that there are similarities in the response of canine and human saphenous vein to stimulation of alpha-2 adrenergic receptors but that the human saphenous vein exhibits essentially no receptor reserve for phenylephrine. We suggest that the lack of receptor reserve for phenylephrine in human saphenous vein explains the greater sensitivity of phenylephrine-induced contractions to antagonism by ntiroglycerin in this tissue.