Endothelium‐dependent relaxation of the pig aorta: relationship to stimulation of ⁸⁶Rb efflux from isolated endothelial cells

Abstract

1 Bradykinin, adenosine triphosphate (ATP) and acetylcholine each relaxed histamine-contracted strips of pig aorta in a dose-dependent manner. These relaxations were abolished when the endothelium was removed. 2 Relaxation induced by ATP was mimicked by adenosine diphosphate (ADP) but adenosine monophosphate (AMP) and adenosine were about 120 times less potent. 3 Relaxation induced by acetylcholine was antagonized by atropine in a competitive manner, and carbachol induced the same degree of relaxation as acetylcholine, but was about 10 times less potent. 4 The calcium ionophore, A23 187, also induced a dose-dependent relaxation of pig aortic strips provided the endothelium was present, suggesting that a rise in the level of ionized calcium within the endothelial cells is one means by which vascular smooth muscle relaxation can be triggered. 5 Bradykinin, ATP, ADP, AMP, adenosine and A23 187 each induced a dose-dependent increase in 86Rb efflux from preloaded pig aortic endothelial cells. The dose-response curves for stimulation of 86Rb efflux and for endothelium-dependent relaxation were similar for each individual compound. ADP was equipotent with ATP, but AMP and adenosine were about 120 times less potent. 6 Neither acetylcholine nor carbachol, in concentrations that induce endothelium-dependent relaxation, had any effect on 86Rb efflux from isolated aortic endothelial cells. 7 Lanthanum, which blocks calcium influx, abolished the increases in 86Rb efflux induced by bradykinin and ATP, and the calcium ionophore A23187 was the most effective stimulant of 86Rb efflux, suggesting that the potassium transport induced by these agents is calcium-activated. 8 It is concluded that endothelial responses to bradykinin and ATP can be assessed by monitoring 86Rb efflux, which probably reflects a calcium-activated efflux of potassium associated with the endothelium-dependent vascular relaxation induced by these agents. This pathway is apparently not involved in endothelial responses to acetylcholine.

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

“…Such a bradykinin-induced relaxation was also found to occur in pig aorta (Gordon & Martin, 1983), in bovine intrapulmonary artery and vein (Gruetter & Lemke, 1986a) and in bovine coronary artery (Angus et al, 1986b). By contrast, the aorta and the renal arteries of neither the cat (Furchgott, 1983) nor the rabbit (Cherry et al, 1982) were relaxed by bradykinin, and in mesenteric arteries of the same species the relaxing effect of bradykinin was proved to be endothelium-independent (Cherry et al, 1982;Forstermann et al, 1986a).…”

Evidence for the involvement of cyclic GMP in adenosine‐induced, age‐dependent vasodilatation

“…In general, the vasodilator effect of adenosine has been Mathieson & Burnstock, 1985;White & Angus, 1987), but in some vessels adenosine caused endothelium-dependent dilatation (Frank & Bevan, 1983;Gordon & Martin, 1983;Rubanyi & Vanhoutte, 1985). We found that in rat aorta, removal of the endothelium considerably attenuated the dilator response to adenosine (Figure 1), as has been shown for the rabbit central ear artery .…”

“…There are, however, data showing that adenosine caused scarcely any dilatation of rat thoracic aorta (White et al, 1985), or was not as effective as adenosine 5'-triphosphate (ATP) in dilating the coronary artery (Gordon & Martin, 1983;White & Angus, 1987). We have observed that dilatation of rat aorta in response to histamine decreased with an increase in age (Moritoki et al, 1986;, and that the ability of the endothelium to produce endothelium-derived relaxing factor (EDRF) in response to histamine, and to form cyclic GMP decreased with age (Moritoki et al, 1988).…”

“…Adenosine has been shown to cause either endotheliumdependent (Gordon & Martin 1983;Kennedy & $urnstock, 1985;Rubanyi & Vanhoutte, 1985) or independent (Collis & Brown, 1983;Mathieson & Burnstock, 1985;White & Angus, 1987) dilatation of various isolated vessels. There are, however, data showing that adenosine caused scarcely any dilatation of rat thoracic aorta (White et al, 1985), or was not as effective as adenosine 5'-triphosphate (ATP) in dilating the coronary artery (Gordon & Martin, 1983;White & Angus, 1987).…”

Endothelium‐dependent and BRL 34915‐induced vasodilatation in rat isolated perfused mesenteric arteries: role of G‐proteins, K+ and calcium channels

“…The evidence for this is derived from the observations that the action of agents that release EDRF is often accompanied by elevation of guanosine 3': 5'-cyclic monophospate (cyclic GMP) levels (Moncada et al, 1988) and can be blocked by inhibitors of guanylate cyclase, methylene blue and oxyhaemoglobin (Murad et al, 1978;Martin et al, 1985). The relative insensitivity of endothelium-dependent effects to guanylate cyclase inhibitors in the rat mesenteric artery (Furchgott et al, 1987) raises the possibility that this effect may be mediated via another mechanism, notably increased potassium permeability as suggested by Bolton et al (1983) through activation of either the Na+/K' pump (Haddy, 1978;Webb & Bohr, 1978;De Mey & Vanhoutte, 1980;Rubanyi & Vanhoutte, 1985) or directly via K+ channels (Gordon & Martin, 1983;Petersen & Maruyama, 1984;Gebremedhin et al, 1987).…”