Influence of the vascular endothelium on agonist‐induced contractions and relaxations in rat aorta

Abstract

1 The influence of the vascular endothelium on agonist-induced contractions and relaxations has been measured using intact segments of rat aorta. Contiguous rubbed segments were used as controls. 2 Angiotensin II, histamine, noradrenaline, U46619 and UK14304 contracted both rubbed and intact tissues. The threshold spasmogenic concentrations of these agonists were lower in rubbed tissues than in intact preparations. 3 The sensitivity and responsiveness of tissues to angiotensin II, histamine, noradrenaline and UK14304 were greater in rubbed than in intact tissues. 4 Acetylcholine and histamine relaxed the established spasms ofintact tissues but not those of rubbed preparations, These relaxant effects of acetylcholine were abolished by pre-incubation with haemoglobin. 5 In the presence of prazosin, noradrenaline or UK 14304 relaxed established contractions in intact tissues. These effects were antagonized by idazoxan or by pre-incubation with haemoglobin. 6 In intact preparations, idazoxan had no effect on the spasmogenic sensitivity and responsiveness to UK14304. 7 Pre-incubation with haemoglobin augmented the spasmogenic actions of noradrenaline, U46619 or UK 14304 in intact tissues, but had no effect on these responses in rubbed preparations. 8 Tissue concentrations of cyclic GMP were greater in intact than in rubbed tissues. A concentration of acetylcholine (10 tiM) evoking just maximal mechanical inhibition produced a significant increase in cyclic GMP concentration in intact preparations. However, no detectable changes in cyclic GMP concentration were produced by UK 14304 (10 !M) or by acetylcholine (30 nM), concentrations which were equi-effective in inhibiting mechanical activity. 9 In the presence of threshold spasmogenic concentrations of noradrenaline, the contractile effects of angiotensin II were augmented and became comparable to those observed in rubbed preparations. In the presence of greater concentrations of noradrenaline, angiotensin II always produced an additional contraction. 10 It is concluded that the presence of the vascular endothelium limits the spasmogenic action of a variety ofagonists. Although spasmogens like noradrenaline and UK 14304 can stimulate the release of endothelium-derived relaxing factor (EDRF) via M2-adrenoceptors, the inhibitory effects of EDRF largely result from the spontaneous release of this substance.

Local formation of angiotensin II in the rat aorta: effect of endothelium

“…Moreover, they demonstrate that the maximal response and the sensitivity of the tissue to All, whether given exogenously or locally formed from AI and TDP renin substrate, were increased by removal of the endothelium. Our observations concerning the influence of the endothelium on the response to exogenous All confirm previous studies performed in the rat aorta and in some other vascular tissues, such as bovine coronary artery, rabbit mesenteric and coeliac arteries (Oshiro et al, 1985;Bullock et al, 1986;Gruetter et al, 1988). However, in other vessels such as rabbit aorta or canine carotid artery, the endothelium has no effect on the contractile response to All (Saye et al, 1984;D'Orleans-Juste et al, 1985).…”

“…In the present study, methylene blue, an inhibitor of EDRF, produced the same potentiation of the contractile response to All as endothelium removal. This indicates that, in the rat aorta, the inhibitory effect of the endothelium on the contraction induced by All may be attributed to the release of EDRF, as has been proposed by Bullock et al (1986) andGruetter et al (1988).…”

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

“…Higher levels of cyclic GMP in unrubbed vessels as compared to those in matched rubbed vessels have been ascribed to the effect of this basal EDRF (Holzmann, 1982;Rapoport & Murad, 1983;Diamond & Chu, 1983;Bigaud et al, 1984;Martin et al, 1986;Spedding et al, 1986;Bullock et al, 1986;Gruetter & Lemke, 1986b). As a consequence, basal levels of cyclic GMP are regarded as an index of the release of basal EDRF.…”

“…Noradrenaline-induced precontractions were 1.98 + 0.60g (0), 1.72 ± 0.44g (0) animal arteries (Cocks & Angus, 1983;Miller & Vanhoutte, 1985;Angus et al, 1986ab;Bullock et al, 1986 and UK 14,304 (0.1 pM-IO pM) were devoid of any relaxing activity (n = 3 and 2, respectively), although the preparations could be relaxed by acetylcholine.…”

Pharmacological features of vascular responses of isolated rat common carotid arteries to vasroactive substances revealed by the cannula insering method.

“…Although xylazine and clonidine did not produce vascular responses in non-pretreated preparations, it is not clear that alpha-2 agonists have vasodilatory effects in preconstricted preparations. It is necessary to examine effects of alpha-2 agonists on preconstricted vascular preparations and/or endothelium rubbed vascular preparations in future, becauses it has been reported that alpha-2 agonists cause vascular relaxations via alpha-2 receptors (Cocks and Angus 1983 ; Angus et al 1986 ;Bullock et al 1986). …”