Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling

Physical inactivity is an independent risk factor for coronary heart disease, yet the mechanism(s) of exercise-related cardioprotection remains unknown. We tested the hypothesis that coronary smooth muscle after exercise training would have decreased mitogen-induced phenotypic modulation and enhanced regulation of nuclear Ca2+. Yucatan swine were endurance exercise trained (EX) on a treadmill for 16–20 wk. EX reduced endothelin-1-induced DNA content by 40% compared with sedentary (SED) swine (P < 0.01). EX decreased single cell peak endothelin-1-induced cytosolic Ca2+ responses compared with SED by 16% and peak nuclear Ca2+ responses by 33% (P < 0.05), as determined by confocal microscopy. On the basis of these results, we hypothesized that sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and intracellular Ca2+ stores in native smooth muscle are spatially localized to dissociate cytosolic Ca2+and nuclear Ca2+. Subcellular localization of SERCA in living and fixed cells revealed a distribution of SERCA nea...