Effect of removing the endothelial cells on the reactivity of rat aortic segments to different ?-adrenoceptor agonists

Abstract

The influence of removing the endothelial cells on the alpha-receptor-mediated contractile response in segments of rat aorta was investigated using agonists with a range of affinity for alpha 1- and alpha 2-receptors. The preferential alpha 1-agonists were methoxamine, cirazoline, ST 587, and Sgd 101/75 and the preferential alpha 2-agonists were B-HT 920, clonidine, and guanfacine. When the endothelium was intact, the intrinsic activity (compared to noradrenaline) varied widely (0.0-0.7) for both groups of agonists. After removal of the endothelium the intrinsic activity was increased in each case to that of noradrenaline, or close to it. Furthermore, an increase in potency was obtained for each agonist, although to different degrees. No correlation, however, was found between the selectivity of the agonists and the degree of enhancement caused by the removal of the endothelium, in terms of either the intrinsic activity or the potency. Moreover, the use of the selective alpha 2-receptor antagonist rauwolscine on intact tissues did not mimic the effect of removing the endothelium. Therefore, the alpha-receptors of the endothelium could not be classified as either of the alpha 1- or alpha 2-subtype.

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

“…Such a role for the vascular endothelium has also been reported in human isolated vessels, particularly human coronary arteries (Thom et al, 1985;Bossaller et al, 1986;Forstermann et al, 1986b). In addition, the presence of endothelium can modulate agonist-induced contractile responses of some animal arteries (Cocks & Angus, 1983;Egleme et al, 1984;Miller et al, 1984;Lues & Schumann, 1984;Godfraind et al, 1985;Carrier & White, 1985;Miller & Vanhoutte, 1985), probably as a consequence of a spontaneous release of ('basal') EDRF (Malta et al, 1986a;Martin et al, 1986). To date, there has been no evidence for basal release of EDRF in human isolated arteries.…”

Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea‐pig pulmonary artery

“…Removal of endothelium increases vasoconstrictor responses to x-adrenoceptor agonists (Cocks & Angus, 1983;Egleme et al, 1984;Lues & Schumann, 1984;Carrier & White, 1985;Martin et al, 1986) and to adrenergic nerve stimulation Cohen & Weisbrod, 1988;Hynes et al, 1988 (Gillespie et al, 1989;Tucker et al, 1990;Li & Rand, 1991), including cerebral arteries (Toda & Okamura, 1990). It is possible that stimulation by EFS of i-NANC nerves, which have been demonstrated in this vessel (Liu et al, 1991b), induces NO release, or alternatively, stimulation of i-NANC nerves releases mediator(s), which act on endothelial cells to stimulate NO release (Liu et al, 1991b).…”

“…Endothelium has an inhibitory effect on the contractile responses to a-adrenoceptor stimulation either by exogenous administration of noradrenaline (Cocks & Angus, 1983) and other aadrenoceptor agonists (Egleme et al, 1984;Lues & Schumann, 1984;Martin et al, 1986) or by adrenergic nerve stimulation in rabbit carotid artery Cohen & Weisbrod, 1988) and rat caudal artery (Hynes et al, 1988). This inhibitory effect of endothelium on the contractile response to adrenergic nerve stimulation is believed to be due to the release of relaxing factor(s) from endothelial cells Tesfamariam & Halpern, 1987;Cohen & Weisbrod, 1988).…”

Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta

“…Recent observations have demonstrated that vascular endothelial cells play an important role in the modification of the actions of contractile agonists in the rat aorta (Egleme et al, 1984;Lues & Schumann, 1984;Carrier & White, 1985;.…”