Endothelial ATP-sensitive potassium channels: a new therapeutic target in cardiovascular medicine?
Recent electrophysiological studies have demonstrated convincingly that ATP-sensitive potassium channels (KATP) are expressed in macro- and microvascular endothelial cells from heart and brain. Several reports have indirectly demonstrated the contribution of endothelial KATP to the regulation of vascular tone, eg, during hypoxia. Experimentally, endothelial KATP can be activated by energy depletion of cells or by adding synthetic potassium channel openers (PCOs). In endothelial cells, in contrast to vascular smooth muscle cells (VSMC), hyperpolarization induced by KATP opening can result in an increase of [Ca2+]i and, further, to enhanced NO and prostanoid synthesis. Although this mechanism is highly speculative, synthetic PCOs, directed against endothelial KATP, may counteract atherogenic stimuli (hypercholesterolemia and hypertension) and/or even suppress symptoms occurring in atherosclerosis (proliferation of VSMC, thrombogenesis). Further-more, the cardioprotective effects of PCOs may be mediated, at least in part, by an activation of endothelial KATP.
Langheinrich
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Bayer AG, PHR-HK 2, Bldg 500, Aprather Weg 18a, D-42096 Wuppertal, Germany. Ulrike.Langheinrich.UL@bayer-ag.de