ENHANCEMENT OF ALPHA-1 AND ALPHA-2 ADRENERGIC AGONIST-INDUCED VASOCONSTRICTION BY REMOVAL OF ENDOTHELIUM IN RAT AORTA

Abstract

Vascular endothelial cell layers play an essential role in the vasodilatory response of several agents. The endothelium may also modulate .alpha. adrenergic agonist-induced vasoconstriction. The responses of rat aortae to selective .alpha.-1 and .alpha.-2 adrenergic agonists were studied. Removal of the endothelium did not significantly alter the maximum contractile response to norepinephrine. The maximum responses to selective .alpha.-1 agonists (phenylephrine and methoxamine) were increased 2-fold. The vasoconstrictor effects of both clonidine and B-HT920 (selective .alpha.-2 agonists) were enhanced 5- to 7-fold after removal of the endothelial cell layer. The sensitivity of the tissue, as reflected by the EC50 [concentration giving 50% effectiveness] value, to each .alpha. adrenergic agonist was enhanced in the absence of endothelium. An explanation for the present results is that .alpha.-1 and .alpha.-2 adrenergic agonists activate adrenoceptors in the endothelial cells and thereby may promote the release of a relaxing factor to inhibit vascular smooth muscle contraction. Removal of the endothelium would abolish release of this putative inhibitory substance and adrenergic agonist would activate only adrenoceptors in the muscle to cause vasoconstriction. Endothelial cells may function as an uptake site for the various adrenergic agonists. Ablation of this uptake process could conceivably result in a greater effective concentration of the agonist in the receptor area and promote a stronger vasoconstrictor effect. The vascular endothelial lining does modulate .alpha. adrenergic agonist-induced vasoconstriction.