Importance of endothelium-derived nitric oxide in porcine coronary resistance arteries

Abstract

Endothelial cells regulate vascular tone through the release of nitric oxide and other relaxing factors. The role of these substances was studied in isolated intramyocardial porcine coronary resistance arteries suspended in myographs for isometric tension recording. The inhibitor of nitric oxide formation NG-monomethyl-L-arginine (L-NMMA; 10(-7)-10(-4)M), but not D-NMMA, caused endothelium-dependent contractions that could be reversed by L-arginine but not by D-arginine. In preparations with endothelium, L-NMMA potentiated the contractions induced by acetylcholine and the relaxations to 3-morpholino-sydnonimine. Under both conditions, the effect of endothelial removal was slightly more pronounced than that of L-NMMA. Bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine evoked endothelium-dependent relaxations. L-NMMA as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) prevented the relaxations induced by clonidine, reduced those to serotonin, but hardly affected those to bradykinin. Thus, in porcine coronary resistance arteries, endothelium-derived nitric oxide is continuously produced from L-arginine. Endothelium-dependent relaxations to clonidine are fully mediated and those to serotonin partially mediated by nitric oxide; its release does not involve a Gi protein. An endothelium-derived relaxing factor different from nitric oxide must mediate the relaxations to bradykinin and contribute to those evoked by serotonin.

Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open‐chest dogs

“…Such an heterogeneous release of EDRF has already been reported in isolated dog coronary arteries (Hoeffner et al, 1989). In isolated small coronary arteries of the pig (Tschudi et al, 1991), and in pressurized mesenteric resistance arteries of the rat (Dohi et al, 1990), administration of L-NMMA induced vasoconstriction, suggesting that these vessels do release nitric oxide from L-arginine under basal conditions, at least in vitro. However, in these experiments, only the larger (>100pum diameter) resistance arteries were studied, and those contribute to less than 50% of total resistance in various vascular beds, including the coronary circulation (Chillian et al, 1986).…”

Stimulation of Bradykinin B 1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

“…The minimal influence of LNA on the CBFv response is consistent with that reported in porcine coronary resistance arteries. 21 This CBFv response to bradykinin, which is resistant to inhibitors of NO synthase, may be mediated by endothelium-derived hyperpolarizing factor (EDHF), because it has been shown that the relaxing response of coronary vessels to bradykinin is also mediated by EDHF, which probably acts through calcium-activated potassium channels. 22,23 However, the in vivo role of EDHF remains unknown because EDHF has not been identified.…”

Cytochrome P450‐dependent effects of bradykinin in the rat heart

“…*P < 0.05; **P < 0.01. (Richard et al, 1990;Cocks & Angus, 1991;Tschudi et al, 1991). Consequently, mediators other than NO, are required to explain the coronary vasodilator effect of BK.…”