Glu298Asp eNOS Gene Polymorphism Causes Attenuation in Exercise‐Induced Muscle Vasodilatation in Humans

We tested the hypothesis that the vasodilatation responses to exercise were attenuated in homozygous individuals for the allele Asp298. Methods: from 287 volunteers genotyped, we studied 24 individuals: Glu/Glu (n=15, age 43±3 yr, BMI 22.9±0.3 kg/m2) and Asp/Asp (n=9, age 40±4 yr, BMI 23.5±0.9 kg/m2). Heart rate (HR), mean blood pressure (MBP) and forearm blood flow (FBF) were recorded during handgrip exercise (30% MVC). Results: FVC responses to exercise were lower in Asp/Asp, compared with Glu/Glu (Δ=0.07±0.14 vs. 0.57±0.09 units, P=.002). To investigate the mechanisms underlying the lowered vasodilatation in Asp/Asp, we studied FBF during L‐NMMA and L‐NMMA + phentolamine in a subset of 8 Glu/Glu and 7 Asp/Asp. We measured muscle sympathetic nerve activity (MSNA). L‐NMMA did not change FVC responses to exercise in Asp/Asp, compared with saline (Δ=−0.05±0.20 vs. −0.09±0.18 units, P=.52). In contrast, L‐NMMA reduced FVC in Glu/Glu (Δ0.79±0.14 vs. 0.14±0.09 units) and the difference between genotypes were no longer observed (P=.62). L‐NMMA + phento increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (Δ=1.16±0.26 vs. 0.56±0.24 units, P=.43). MBP and MSNA were similar among genotypes. Conclusion:Asp/Asp individuals have attenuated muscle vasodilatation responsiveness to exercise, which seems to be primarily mediated by a reduced nitric oxide bioavailability.