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

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 alpha, the cumulative addition of bradykinin caused a concentration-dependent relaxation during contractions evoked by prostaglandin F2 alpha, 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.