Enhancement of alpha-1 and alpha-2 adrenergic agonist-induced vasoconstriction by removal of endothelium in rat aorta.

It is well known that the vascular endothelial cell layer plays an essential role in the vasodilatory response of several agents. In this study we have investigated the possibility that 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. However, 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 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. On the other hand, 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 thus promote a stronger vasoconstrictor effect.(ABSTRACT TRUNCATED AT 250 WORDS)