Vasopressin V1a receptor gene and voluntary exercise in humans and Mice

Abstract

Exercise training protects against age- and lifestyle-related diseases. We recently reported that middle-aged and older Japanese men carrying the TT genotype of the single nucleotide rs1042615 polymorphism in the vasopressin V1a receptor had significantly higher body mass index and diastolic blood pressure than those who did not. However, these higher values decreased to levels comparable to those of men carrying other genotypes following 5 months of interval walking training (IWT), suggesting that they might have been physically inactive before starting IWT. Therefore, we postulated that TT men would have lower adherence to longterm exercise programs. To assess this, middle-aged and older men underwent IWT for 29 months. We found that adherence to the exercise program was markedly decreased in TT men compared with men of other genotypes during the training period. To elucidate the mechanism, we assessed whether voluntary locomotion was impaired in mice genetically deficient in V1a receptors (V1a KO). We found that voluntary locomotion in wild-type mice occurred at higher probability after cerebral activation, while in V1a KO mice the probability was markedly reduced with no suppression of baroreflex control of heart rate during cerebral activation. Moreover, these findings in V1a KO mice were confirmed after local infusion of a V1a receptor antagonist into the nucleus tractus solitarii of wild-type mice. Thus, central V1a receptors play an important role in facilitating voluntary exercise. This finding might help to explain the lower adherence to a long-term IWT program in TT men.