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Increased Ca 2+ sensitization in collateral‐dependent coronary arterioles of exercise trained swine: role of Rho‐kinase
Author(s) -
Heaps C L,
Mattox M L,
Sturek M,
Parker J L
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.a730-a
Subject(s) - medicine , contraction (grammar) , cardiology , arteriole , sensitization , isometric exercise , endocrinology , anatomy , circulatory system , immunology
Exercise training increases Ca 2+ ‐dependent basal active tone in coronary arterioles distal to chronic occlusion (collateral‐dependent). In the present study, we tested the hypothesis that agonist‐mediated contractile responses in collateral‐dependent coronary arterioles of exercise trained pigs would be enhanced and attributable to Ca 2+ sensitization. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniswine. Arterioles (~150 μm ID) were isolated from both the collateral‐dependent and nonoccluded regions of sedentary (SED; pen‐confined) and exercise trained (EX; treadmill; 14 wks) pigs and studied using microvessel myographs and standard isometric techniques. Contraction to endothelin‐1 in collateral‐dependent arterioles was not altered in SED animals, but in EX pigs displayed enhanced constriction vs. nonoccluded arterioles. Importantly, simultaneous measures of endothelin‐mediated tension and myoplasmic free Ca 2+ (fura‐2) revealed enhanced Ca 2+ sensitivity in collateral‐dependent arterioles of EX animals. Further, inhibition of Rho‐kinase (Y‐27632; 1 μM) reversed the enhanced contraction in collateral‐dependent arterioles of EX pigs. Taken together, our data indicate that coronary arterioles isolated from the collateral‐dependent region of EX animals display increased endothelin‐stimulated contraction that is attributable to Rho‐kinase‐mediated Ca 2+ sensitization. Support: NIH HL64931, HL62552