Endothelium-dependent hyperpolarization caused by bradykinin in human coronary arteries.

Abstract

The present study was designed to determine whether bradykinin induces endothelium-dependent hyperpolarization of vascular smooth muscle in human coronary arteries, and if so, to define the contribution of this hyperpolarization to endothelium-dependent relaxations. The membrane potential of arterial smooth muscle cells (measured by glass microelectrodes) and changes in isometric force were recorded in tissues from six patients undergoing heart transplantation. In the presence of indomethacin and NG-nitro-L-arginine (NLA), the membrane potential was -48.3±0.6 and -46.9±0.6 mV, in preparations with and without endothelium, respectively, and was not affected by treatment with perindoprilat, an angiotensin-converting enzyme inhibitor. In the presence of both indomethacin and NLA, bradykinin evoked transient and concentration-dependent hyperpolarizations only in tissues with endothelium, which were augmented by perindoprilat and mimicked by the calcium ionophore A23187. Glibenclamide did not inhibit membrane hyperpolarization to bradykinin. In rings contracted with prostaglandin F2,, the cumulative addition of bradykinin caused a concentration-dependent relaxation during contractions evoked by prostaglandin F2, which was not abolished by NLA and indomethacin. The present findings demonstrate the occurrence of endothelium-dependent hyperpolarization, and its contribution to endothelium-dependent relaxations, in the human coronary artery. (J. Clin. Invest. 1993. 92:2867-2871

Mechanisms of L‐NG nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries

“…In Tyrode solution, ouabain and a decrease in [Na+le had much less effect on L-N' nitroarginineresistant relaxation of BCA; this has been also shown in guineapig coronary arteries (Chen & Cheung, 1992), rat mesenteric arteries (Ayotunde et al, 1991) and human coronary arteries (Nakashima et al, 1993). Since the inhibitory properties of ouabain and a reduced [Nal]e critically depend on the solutions used, the effect observed with PBS is more likely due to some depolarizing effect of ouabain and reduced [Nal]e rather than interference with EDHF directly.…”

Upregulation of endothelium-derived hyperpolarizing factor compensates for the loss of nitric oxide in mesenteric arteries of dahl salt-sensitive hypertensive rats

“…[39][40][41][42] Although few studies have investigated the role of EDHF in human hypertension, Taddei et al 41 have reported that EDHF partially compensates for the loss of NO to sustain endothelium-dependent vasodilation in patients with essential hypertension. With regard to salt-sensitive hypertensive patients, several studies have reported that impairment of the NO pathway is associated with endothelial dysfunction; 43,44 however, the role of EDHF in endothelial function in salt-sensitive hypertensive individuals remains unresolved and thus warrants further investigation.…”

Display of the characteristics of endothelium‐derived hyperpolarizing factor by a cytochrome P450‐derived arachidonic acid metabolite in the coronary microcirculation

“…Although endothelium-dependent hyperpolarization has been demonstrated in bovine, porcine and human epicardial coronary arteries in vitro Nakashima et al, 1993) the chemical nature of this factor is still unclear. Moreover, the role of EDHF in the coronary microcirculation remains to be established.…”