CaM Kinase II and Ca2+ sensitization mediate enhanced KCl constriction in collateraldependent coronary arteries of both sedentary and exercisetrained pigs
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abstract
The purpose of this study was to determine mechanisms underlying enhanced KClmediated constriction in collateraldependent coronary arteries of sedentary (SED) and exercisetrained (ET) pigs subjected to chronic occlusion. Ameroid constrictors were surgically placed around the left circumflex artery of female Yucatan miniature swine. Eight weeks postoperatively, pigs were randomized into SED (penconfined) or ET (treadmill run; 5 days/week; 14 weeks) groups. Arteries (150300m luminal diameter) were isolated from the collateraldependent and control (nonoccluded) myocardial regions. Contractile tension and simultaneous measures of tension and intracellular free Ca2+ levels ([Ca2+]i; fura2) were measured in response to increasing concentrations of KCl. Chronic occlusion enhanced contractile responses to KCl and increased tension at comparable levels of [Ca2+]i in collateraldependent compared to control arteries of both SED and ET pigs. Inhibition of CaMKII (1M), but not of Rhokinase (Y27632; 10M or hydroxyfasudil; 30M) or PKC (calphostin C; 1M), abolished the enhanced contractile responses to KCl. Taken together, these data reveal that chronic coronary occlusion leads to enhanced contractile responses to KCl in collateraldependent coronary arteries likely via an increase in CaMKIImediated Ca2+ sensitization that is not corrected with ET.
