Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries

Abstract

Endothelial cells release nitric oxide from L-arginine, and this pathway can be inhibited by the analogue of L-arginine, NG-monomethyl-L-arginine (L-NMMA). The effect of L-NMMA on endothelium-dependent relaxation of epicardial porcine coronary arteries was studied in isolated blood vessels suspended in organ chambers for isometric tension recording. Endothelium-dependent relaxations to bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine were evaluated in the presence and absence of L-NMMA (10(-5)-10(-3) M). L-NMMA, as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) and hemoglobin (10(-5) M), inhibited endothelium-dependent relaxation to serotonin and clonidine. The effect of L-NMMA could be reversed by L-arginine but not by D-arginine. In contrast, L-NMMA, methylene blue, and hemoglobin caused a weak inhibition of the endothelium-dependent relaxation evoked by bradykinin; indomethacin and tranylcypromine had no effect. The inhibitor of Gi proteins pertussis toxin (100 ng/ml) abolished the relaxations evoked by clonidine and markedly reduced those evoked by serotonin but did not affect those caused by bradykinin. In the presence of pertussis toxin, L-NMMA induced a further reduction of the relaxations to serotonin, suggesting that inhibition of Gi proteins does not completely prevent the activation of the L-arginine pathway. Thus endothelium-dependent relaxations to serotonin and to the alpha 2-adrenergic agonist clonidine are mediated through the release of nitric oxide formed from L-arginine in endothelial cells, whereas bradykinin evokes endothelium-dependent relaxations via a different pathway.

Evidence for differential roles of nitric oxide (NO) and hyperpolarization in endothelium‐dependent relaxation of pig isolated coronary artery

“…In fact, Nagao & Vanhoutte (1992a) Nagao & Vanhoutte (1992a) interpreted the reduction in potency and maximum response to BK in the presence of high K+ as due to inhibition of the effects of hyperpolarization and concluded that hyperpolarization, not NO, is the main factor involved in endothelium-dependent relaxation in the pig coronary artery. Similar conclusions were reached by Richard et al (1990), Pacicca et al (1992 and Adeagbo & Triggle (1993). Our study, in which any complications of functional antagonism were avoided, suggests the opposite, that NO is the main relaxing factor with hyperpolarization providing 'back-up' if the NO/NOS system fails.…”

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.…”

Working under pressure: the vascular endothelium in arterial hypertension

“…98 Since under these conditions vascular smooth muscle cells become hyperpolarized, an endotheliumdependent hyperpolarizing factor (EDHF) of unknown chemical structure has been proposed ( Figure 1). 99,100 There is evidence that a calciumdependent potassium channel on endothelial or smooth muscle cells is important in mediating endoJournal of Human Hypertension thelium-dependent hyperpolarization, a mechanism that is impaired in arterial hypertension.…”