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Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries

Departments of Anesthesiology and Physiology, Medical College of Wisconsin, and Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin

Submitted 14 June 2004 ; accepted in final form 10 September 2004

Vasoconstriction via ₂-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 ,-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 ,-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 ,-methylene ATP) and lowest with pH 7.0 (–4.9 ± 0.10 log M ,-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 ,-methylene ATP (n = 6). There was no effect of pH on phenylephrine dose-response curves. These data indicate that the vasoconstrictor response to ,-methylene ATP is sensitive to pH and that lower pH attenuates the response of P2X purinergic receptors.

hydrogen ion; vascular smooth muscle; pH

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