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The interaction between genes and environment can influence cardiovascular disease (CVD). This 16 month study investigated if genes associated with cardiovascular (CV) regulation were expressed differently in animals having: 1) no access to physical activity or exercise (SED), 2) access to hour-long, twice weekly activity (PA), and 3) access every-other-day to a running wheel (EX). Out of 31,000 genes, a CV subset comprising 44 genes was investigated. Ten genes from this subset were expressed differently in EX compared with SED, and 34 genes were expressed differently in PA compared with SED (p<0.05). Total cholesterol (70±8 vs. 101±9 mg dl⁻¹), triglycerides (104±8 vs. 127±4 mg dl⁻¹), resting systolic blood pressure (130±3 vs. 141±3 mmHg), mean arterial pressure (110±2 vs. 120±2 mmHg) and heart rate (380±6 vs. 405±9 beats min⁻¹) were lower in EX compared with SED (p<0.05), but intracellular …