The Influence Of Physical Activity And Exercise On Physiological Markers And Genetic Determinants Of Blood Pressure

Abstract

The interaction of genetics and environment play a major role in health and disease. Physical activity Influences the expression of specific sets of gene that regulate critical physiological functions. Modeling experiments to investigate gene-environment interaction in a laboratory setting would provide the opportunity to gain mechanistic insight under controlled conditions. In laboratory research it is unclear if the gene-environment interaction of a sedentary lifestyle predisposes laboratory animals to hypokinetic diseases such as hypertension. PURPOSE We sought to compare gene expression and physiological markers of hypertension in animals with: i. A sedentary lifestyle in a standard cage (SED); ii. access to twice-weekly physical activity in a large box outside a standard cage (PA); and iii. access to regular exercise in cages with running wheels (EX). METHODS The GeneChip® Rat Genome 230 2.0 Array was used for comprehensive screening of the transcribed rat genome on a single array. Here, we report results related to genes directly associated with hypertension. Blood pressure was measured by a tail-cuff sphygmomanometer. RESULTS Systolic blood pressure (SBP) was highest in the SED (140.6±3.1 mmHg) vs. EX (129.8±2.6 mmHg, F 1,28 =6.33, p < 0.05). Mean SBP and mean gene expressions showed the following significant correlations: SBP and farnesyl diphosphate farnesyl transferase 1 (Fdft1), r =0.95;SBP and very low-density lipoprotein receptor (Vldlr) r =0.52; and SBP and gap junction membrane channel protein alpha 1 (Gja1), r =0.36, p < 0.05. Fdft1, a regulator of lipid biosynthesis, was highest in SED followed by PA and EX (5713±101 vs. 5527±385 vs. 5097±145). Vldlr, a regular of cholesterol metabolism and lipid transport, was lower in SED vs PA (6899±144 vs. 7782±333, p < 0.05). Gja1, a regulator of cell signaling and heart rate, was lower in SED compared with EX (324±62 vs. 366.7±75, p < 0.05). CONCLUSIONS These results indicate that a sedentary environment can induce hypertension and that certain blood pressure-regulating genes are expressed differently in SED compared to animals with access to either PA or EX. Supported by NIH Grant 1 R15 AG 20526–01A1.