Chronic hypoxia augments depolarization-induced Ca2+ sensitization in pulmonary vascular smooth muscle through superoxide-dependent stimulation of RhoA.

ABSTRACT: Rho kinase (ROCK)-dependent vasoconstriction has been implicated as a major factor in chronic hypoxia (CH)-induced pulmonary hypertension. This component of pulmonary hypertension is associated with arterial myogenicity and increased vasoreactivity to receptor-mediated agonists and depolarizing stimuli resulting from ROCK-dependent myofilament Ca(2+) sensitization. On the basis of separate lines of evidence that CH increases pulmonary arterial superoxide (O(2)(-)) generation and that O(2)(-) stimulates RhoA/ROCK signaling in vascular smooth muscle (VSM), we hypothesized that depolarization-induced O(2)(-) generation mediates enhanced RhoA-dependent Ca(2+) sensitization in pulmonary VSM following CH. To test this hypothesis, we determined effects of the ROCK inhibitor HA-1077 and the O(2)(-

SUBMITTER: Broughton BR 

PROVIDER: S-EPMC2822557 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature