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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 283; no. 6; pp. H2397 - H2410
• Main Authors: Wamhoff, B. R, Bowles, D. K, Dietz, N. J, Hu, Q, Sturek, M
• Format: Journal Article
• Language: English
• Published: United States 01.12.2002
• Subjects: Animals; Bromodeoxyuridine; Caffeine - pharmacology; Calcium - metabolism; Calcium Signaling - physiology; Calcium-Transporting ATPases - metabolism; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Cell Separation; Coronary Vessels - cytology; Coronary Vessels - drug effects; Coronary Vessels - metabolism; DNA - metabolism; Endothelin-1 - pharmacology; Female; Fluorescent Dyes; In Vitro Techniques; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - ultrastructure; Phenotype; Physical Conditioning, Animal; Physical Exertion - physiology; Sarcoplasmic Reticulum - metabolism; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine, Miniature
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00371.2001

1  Departments of Physiology and 2  Internal Medicine, School of Medicine, 3  Department of Veterinary Biomedical Sciences, School of Veterinary Medicine, 4  Dalton Cardiovascular Research Center, and 5  Diabetes and Cardiovascular Biology Program, University of Missouri, Columbia, Missouri 65212 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 Ca 2+ . 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 Ca 2+ responses compared with SED by 16% and peak nuclear Ca 2+ responses by 33% ( P  < 0.05), as determined by confocal microscopy. On the basis of these results, we hypothesized that sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) and intracellular Ca 2+ stores in native smooth muscle are spatially localized to dissociate cytosolic Ca 2+ and nuclear Ca 2+ . Subcellular localization of SERCA in living and fixed cells revealed a distribution of SERCA near the sarcolemma and on the nuclear envelope. These results show that EX enhances nuclear Ca 2+ regulation, possibly via SERCA, which may be one mechanism by which coronary smooth muscle cells from EX are less responsive to mitogen-induced phenotypic modulation. endothelin-1; sarco(endo)plasmic reticulum Ca 2+ -ATPase; electron microscopy; fluorescence microscopy; swine Deceased 7 May 2002.