The diameter of resistance arteries, and thus, tissue perfusion and blood pressure, is tightly regulated through the integrated activity of endothelial and smooth muscle cells, and sympathetic nerves. The endothelium regulates the contractility of smooth muscle cells by releasing diffusible factors such as nitric oxide (NO) and via gap junction-mediated electrical coupling; opening of endothelial Ca 2+ -activated K + (KCa) channels causes hyperpolarization which spreads to underlying smooth

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... le cells to reduce opening of voltage-dependent Ca 2+ channels, decrease Ca 2+ influx and so limit contraction. The bioavailability and therefore, biological activity, of NO is determined by its interaction with the free radical superoxide anion (O2 -), elevated levels of which are associated with risk factors for cardiovascular disease. Traditionally, NO and endothelium-dependent smooth muscle hyperpolarization have been regarded as two separate mechanisms for regulation of arterial diameter. However, several lines of recent evidence support the proposal that NO bioavailability and KCa channel activity may be linked: 1. Exposure of endothelial cells to shear stress results in activation of both small conductance KCa channels and increased NO production. 2. Agonist-evoked NO production and