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Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 (AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18-35 years. Blood samples (n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC (n = 45) and CT (n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (-40+/-4% vs. -24+/-3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+69+/-9% vs. +42+/-9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

Background: The purpose of the present study was to determine interactive and main effects of the eNOS T-786C gene polymorphism and habitual physical activity level on forearm vascular resistance (FVR) and forearm blood flow (FBF) at rest and during 3 min of reactive hyperemia., Methods: We studied healthy, Caucasian (age 25 +/- 1 yr), sedentary (maximal oxygen consumption, [OV0312]O2max: 33.8 +/- 1 mL x kg(-1)x min(-1)), and endurance-trained ([OV0312]O2max: 45.3 +/- 1 mL x kg(-1)x min(-1)) women. FBF was measured using venous occlusion plethysmography before (resting) and after 5 min of arm arterial occlusion at 1 (peak vasodilation), 2, and 3 min of reactive hyperemia. [OV0312]O2max was measured using a standard treadmill protocol, and skinfolds were measured to estimate body composition., Results: There was a significant interaction between eNOS genotype and physical activity level on resting FVR (P = 0.0003). Sedentary subjects with the TT genotype had the lowest resting FVR, but among the endurance-trained group, the TC+CC genotype group had the lowest resting FVR. This interaction was reflected in the resting FBF values (P = 0.03). After accounting for important covariates, there was a main effect of eNOS genotype on peak FBF (TT, 7.0 +/- 0.3 vs TC+CC, 5.9 +/- 0.4 mL x 100 mL(-1) FAV x min(-1), P = 0.03) and the percent decrease in FVR (TT, -62 +/- 2 vs TC+CC, -51 +/- 4%, P = 0.04) at minute 1., Conclusions: These results of the interactive effects suggest that young females possessing a C allele may reduce their resting FVR by improving their cardiovascular fitness level, but TT homozygotes, who may have normal eNOS gene function, may not improve their resting FVR with improvements in cardiovascular fitness. Furthermore, regardless of physical activity level, the TT genotype showed a favorable hemodynamic response during reactive hyperemia compared with the C allele carriers.