Maxi-K+ channel beta1 expression in sleep apnea patients and its modulation by CPAP treatment.

Background: Maxi-K(+) channels play a major vasodilator role in the regulation of arterial tone. Hypoxia downregulates the expression of the maxi-K(+) channel beta1-subunit in rat and human arterial myocytes, thus facilitating vasoconstriction. We have investigated the relationships among hypoxemia, arterial pressure, and the expression of the beta1-subunit in patients with severe obstructive sleep apnea-hypopnea syndrome (SAHS), a highly prevalent condition that predisposes to hypertension.

Role of peroxynitrite in endothelial damage mediated by Cyclosporine A.

Although Cyclosporine A (CsA) is an effective therapy for immunosuppression, its use encompasses serious side effects that have been associated with oxidative stress. We previously reported the intracellular formation of both peroxynitrite and 3-nitrotyrosine in cultured bovine aortic endothelial cells (BAEC) when exposed to CsA. Here we show that re-addition of CsA to BAEC increases peroxynitrite formation in a concentration-dependent manner.

Decreased expression of maxi-K+ channel beta1-subunit and altered vasoregulation in hypoxia.

Background: Hypertension, a major cause of cardiovascular morbidity and mortality, can result from chronic hypoxia; however, the pathogenesis of this disorder is unknown. We hypothesized that downregulation of the maxi-K+ channel beta1-subunit by hypoxia decreases the ability of these channels to hyperpolarize arterial smooth muscle cells, thus favoring vasoconstriction and hypertension.

Methods And Results: Lowering O2 tension produced a decrease of maxi-K+ beta1-subunit mRNA levels in rat (aortic and basilar) and human (mammary) arterial myocytes.

Superoxide limits cyclosporine-A-induced formation of peroxynitrite in endothelial cells(2).

Peroxynitrite (ONOO(-)) is a potent oxidant formed by the nonenzymatic reaction between superoxide anion (O(2)(*-)) and nitric oxide (NO*) in a one-to-one stoichiometry. Accumulated evidence suggests that endothelial dysfunction coincides with an enhanced NO* synthase expression and O(2)(*-) production, facilitating ONOO(-) formation. In vivo, formation of ONOO(-) has been associated with atherosclerosis and vascular aging.