Membrane depolarization is required for pressure-dependent pulmonary arterial tone but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia

Membrane depolarization is required for pressure-dependent pulmonary arterial tone but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia

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Enhanced vasoconstriction is increasingly identified as an important contributor to the development of pulmonary hypertension.Chronic hypoxia results in enhanced Rho kinase mediated Ca 2+ sensitization contributing to pressure-dependent pulmonary arterial tone as well as augmented vasoconstriction to endothelin-1 and depolarizing stimuli.We sought to investigate the interaction between these vasoconstrictor stimuli in isolated, pressurized, pulmonary arteries.We used the K + ionophore, valinomycin, to clamp membrane potential (V m ) to investigate the role of membrane depolarization borstlist självhäftande in endothelin-1 and pressure-dependent constriction, and endothelin-1 receptor inhibitors to determine whether membrane depolarization or stretch signal through endothelin-1 receptors.

Clamping V m prevented pressure-dependent tone, but not enhanced vasoconstriction to endothelin-1 following chronic hypoxia.Furthermore, endothelin-1 receptor inhibition had no effect on either pressure-dependent tone or vasoconstriction to KCl.As Src kinases contribute to both pressure-dependent tone and enhanced endothelin-1 vasoconstriction following chronic stuart products emcelle tocopherol hypoxia, we further investigated their role in depolarization-induced vasoconstriction.Inhibition of Src kinases attenuated enhanced vasoconstriction to KCl.

We conclude that membrane depolarization contributes to pressure-dependent tone but not enhanced vasoconstriction to ET-1, and that Src kinases serve as upstream mediators facilitating enhanced Rho kinase-dependent vasoconstriction following chronic hypoxia.