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.

Nitrosative stress by cyclosporin A in the endothelium: studies with the NO-sensitive probe diaminofluorescein-2/diacetate using flow cytometry.

Background: We have reported previously that exposure of endothelial cells to cyclosporin A (CsA) may result in the regulation of specific genes, such as the endothelial nitric oxide synthase. In the context of endothelial toxicity, whether this represents an adaptive response to injury at the physiological level or contributes further to the generation of nitrosative stress remains to be investigated. The precise reactive species potentially produced by CsA and their capacity to modify proteins functionally are not well known.