Enhanced response of pig coronary arteries to endothelin-1 after ischemia–reperfusion. Role of endothelin receptors, nitric oxide and prostanoids

Working under pressure: coronary arteries and the endothelin system

“…Since most clinical data have been collected in an elderly population, most likely showing some degree of endothelial dysfunction, it is quite possible that our understanding of ET-1 function as a proconstrictor and proinflammatory factor is only a reflection of these data and thus may not illustrate the effects of ET-1 in young and healthy subjects. In support of this statement, the induction of an endothelial damage eliminates ET B receptordependent relaxation in pig coronary arteries (19). The seminal demonstration that ACh induces a contraction of coronary arteries in patients with CAD but a dilation otherwise (49), is a good example of such a case.…”

“…Similarly, the injection of ET-1 in isolated rat hearts leads to a drop in coronary perfusion pressure at low concentrations of ET-1 (15). In coronary arterial rings isolated from young and healthy pigs, the activation of endothelial ET B receptors induces a significant relaxation (19) through the release of NO and prostacyclin (17,56). In addition, we know that in the human forearm circulation, the increase in blood flow induced by ET A receptor blockade is blunted by ET B receptor antagonism and NOS inhibition (70).…”

“…The greatest improvement associated with the intracoronary infusion of the ET A receptor antagonist was observed in patients with the greatest endothelial dysfunction (34), suggesting that ET-1 contributes to the acute inactivation of NO. In porcine coronary arteries subjected to ischemia reperfusion injury, another model of endothelial dysfunction, the vasoreactivity to exogenous ET-1 was increased and associated with a reduction in endothelial ET B receptor-mediated dilation and an increase in vascular smooth muscle ET B receptor-dependent contraction (19). Böhm et al reported that both the selective ET A receptor (BQ123) antagonist and the combination of selective ET A (BQ123) and ET B receptor (BQ788) antagonists improved endothelium-dependent dilation in the coronary arteries of patients with CAD (11).…”

New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus

“…Previous studies on experimental animal models have demonstrated that ET receptor antagonists ameliorate myocardial ischaemia-reperfusion injury by reducing infarct size and improving post-ischaemic endotheliumdependent vasodilatation (Pernow and Wang, 1997). The mechanism behind the contribution of ET-1 to ischemia-reperfusion injury may be related to increased coronary vasoconstrictor effect of ET-1 (Climent et al, 2005), increased accumulation of neutropils in the reperfused myocardium (Gonon et al, 2004), reduced expression of endothelial NO synthase (Gonon et al, 2004) and production of ROS. The effect of the dual ET A /ET B receptor antagonist bosentan was tested in a human model of ischaemia-reperfusion injury in the forearm.…”

Endothelium-derived endothelin-1

“…The patients with the greatest endothelial dysfunction benefited the most from the intracoronary infusion of the ET A antagonist [63]. In pig coronary arteries subjected to ischemia reperfusion, another model of endothelial dysfunction, the vasoreactivity to exogenous ET-1 was increased and associated with a reduction in endothelial ET B -mediated dilation and an increase in vascular smooth muscle ET B -dependent contraction [78]. Bohm et al reported that both selective ET A (BQ123) and the combination of selective ET A (BQ123) and ET B (BQ788) antagonists improved endothelial-dependent dilation in coronary arteries from patients with CAD [61].…”