Effects of Aging on Purinergic Vasoconstriction in Skeletal Muscle Arterioles

There is strong evidence that ATP acts as a neurotransmitter via the purinergic P2 receptor (P2X) and is co‐released with norepinephrine from the sympathetic nerves in skeletal muscle. The effect of old age on purinergic‐mediated signaling remains unknown. We tested the hypothesis that skeletal muscle P2X receptor‐mediated vasoconstriction is diminished with advancing age. First‐order (1A) arterioles (~115 μm) from the soleus muscle of young (Y, ~6 mo; n =8) and old (O, ≥ 24 mo; n = 9) male Fischer‐344rats were isolated and cannulated. Concentration‐response relations to the cumulative addition of ATP (10 −9 to 10 −4 M) were determined and normalized to maximal diameter. P2X receptor mRNA expression was determined using real‐time PCR. There was an age‐related reduction in maximal vasoconstriction to ATP (Y, 43.7 ± 8.8%, O, 12.23 ± 8.0%; P<0.05). Further, with old age there was a reduction in the expression of P2X receptor mRNA in soleus muscle arterioles. These data demonstrate that advancing age diminishes purinergic vasoconstriction to ATP in skeletal muscle arterioles and this decrement is associated with a reduced expression of P2X receptor mRNA. These age‐related reductions in purinergic signaling may contribute to the altered distribution of skeletal muscle blood flow during exercise and orthostatic challenges. Supported by NIH grant AG‐031327.