Abstract

75 The mechanisms underlying enhanced myogenic contraction (MC) in coronary resistance arteries isolated from exercise-trained (ET) pigs are unknown. The purpose of this study was to test the hypothesis that ET-induced adaptations in protein kinase C (PKC) signaling underlie enhanced MC. Male Yucatan miniature swine (n=7) trained 75% of VO2max for 16 weeks (6 mph, 10% grade, 60 min) or remained sedentary (SED; n=6). Vasoreactivity was evaluated in cannulated resistance arteries (100 μm) in response to intraluminal pressure (60, 75, 90 cmH2O) or potassium chloride (KCL; 60 mM) with and without the PKC blocker chelerythrine (CE; 10 μM). Diameter measurements were expressed relative to passive diameter (after 100 μM sodium nitroprusside). CE elicited greater reductions in MC in ET vs SED (p<0.01). At 90 cmH2O, CE decreased MC by 44% vs 25% in ET and SED, respectively (p<0.01). KCL constriction was also less in ET vs SED (18% vs 34%; p<0.01). Western blotting revealed significant increases in PKC-α but not PKC-∊ levels in resistance arteries isolated from ET. Interestingly, voltage-gated Ca2+ current was blocked by CE in cells isolated from resistance arteries. These data suggest that PKC-dependent effects on MC are greater in resistance arteries isolated from ET. These data further suggest that effects on MC may be mediated, at least in part, by ET effects on PKC-dependent modulation of voltage-gated Ca2+ channels. (Supported by NIH grants PO1-HL-52490 and T32-HD-07460-04).

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