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Contribution of Rho Kinase to Elevated Basal Pulmonary Arterial Tone Following Chronic Hypoxia
Author(s) -
Broughton Brad R.S.,
Walker Benjimen C.,
Resta Thomas R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a403-b
Subject(s) - rho associated protein kinase , basal (medicine) , vasodilation , hypoxia (environmental) , medicine , endocrinology , rhoa , coronary arteries , protein kinase c , circulatory system , chemistry , anatomy , artery , kinase , signal transduction , biochemistry , oxygen , organic chemistry , insulin
Previous studies have demonstrated enhanced basal tone in pulmonary arteries following chronic hypoxia (CH). Furthermore, basal RhoA activity and Rho kinase (ROK) expression levels are augmented in CH intrapulmonary arteries. We hypothesized that Rho kinase mediated Ca 2+ sensitization contributes to increased basal tone in pulmonary arteries from CH rats. To test this hypothesis, we assessed the contribution of vascular smooth muscle (VSM) Ca 2+ sensitization pathways to basal tone in endothelium‐denuded, pressurized pulmonary arteries (184 ± 6 μm inner diameter) from control and CH (4 wk at 0.5 atm) rats. Arteries were loaded with fura‐2 AM to continuously monitor VSM [Ca 2+ ] i . Basal VSM [Ca 2+ ] i was not different between groups. The NO donor spermine NONOate (1 μM), which had little vasodilatory influence in control arteries (0.6 ± 0.3 % reversal of baseline inner diameter), induced a 21.8 ± 4.3 % vasodilatory response in CH arteries without a significant change in VSM [Ca 2+ ] i . In addition, the Rho kinase inhibitor Y‐27632 (10 −7 –10 −5 M), caused a concentration‐dependent reversal of basal tone in CH vessels (8.5 ± 1.6 % at 10 −5 M), but had little effect in control arteries (1.3 ± 0.3 % at 10 −5 M). Interestingly, Y‐27632 decreased VSM [Ca 2+ ] i in a concentration‐dependent manner in both control and CH vessels. In contrast, the protein kinase C (PKC) inhibitor GF‐109203X (1 μM) did not significantly affect baseline inner diameter or [Ca 2+ ] i in either group. We conclude that ROK, but not PKC, may contribute to elevated basal tone in pulmonary arteries from CH rats through both Ca 2+ ‐dependent and ‐independent mechanisms.