Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries

Vasoconstriction via α₂-receptors is known to be sensitive to acidic pH, but little is known about the pH sensitivity of P2X receptors. ATP is a cotransmitter released with norepinephrine from the sympathetic nerves and causes vasoconstriction via P2X purinergic receptors on vascular smooth muscle. We hypothesized that reductions in pH would attenuate P2X-mediated vasoconstriction in iliofemoral artery rings. Twenty-five rats were killed, and the iliac and femoral arteries were dissected out and placed in modified Krebs-Henseleit buffer. The arteries were cut into 2-mm sections and mounted in an organ tissue bath. Tension (g) was measured during a potassium chloride and norepinephrine challenge (maximal tension). The arteries were then exposed to α,β-methylene ATP (10^-7-10^-3 M; n = 13) or phenylephrine (10^-7-10^-4 M; n = 6) with a tissue bath pH of 7.8, 7.4, and 7.0. Dose-response curves were fit with nonlinear regression analysis to calculate the EC₅₀ and slope. The peak tension with α,β-methylene ATP was lower during pH 7.0 (1.37 ± 0.09 g) compared with pH 7.8 (1.90 ± 0.12 g). EC₅₀ was highest with pH 7.4 (-5.38 ± 0.18 log M α,β-methylene ATP) and lowest with pH 7.0 (-4.9 ± 0.10 log M α,β-methylene ATP). The slopes of the dose-response curves were not different. Pyridoxal phosphate-6-azo(benzene-2,4- disulfonic acid) abolished contraction caused by the addition of α,β-methylene ATP (n = 6). There was no effect of pH on phenylephrine dose-response curves. These data indicate that the vasoconstrictor response to α,β-methylene ATP is sensitive to pH and that lower pH attenuates the response of P2X purinergic receptors.