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Am J Physiol Heart Circ Physiol (September 16, 2004). doi:10.1152/ajpheart.00574.2004
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Submitted on June 14, 2004
Accepted on September 10, 2004

Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries

Heidi A Kluess, John B Buckwalter, Jason J Hamann, and Philip S Clifford*

* To whom correspondence should be addressed. E-mail: pcliff{at}mcw.edu.

Vasoconstriction via {alpha}-2 receptors are known to be sensitive to acidic pH, but little is known about the pH sensitivity of P2X receptors. ATP is a co-transmitter 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 sacrificed, the iliac and femoral arteries dissected out, and placed in modified Krebs-Henseleit buffer. The arteries were cut into 2mm sections and mounted in an organ tissue bath. Tension (grams) was measured during a potassium chloride and norepinephrine challenge (maximal tension). The arteries were then exposed to {alpha},{beta}-methyleneATP (10-7 to 10-3M; n=13), or phenylephrine (10-7 to 10-4M; n=6) with tissue bath pH of 7.8, 7.4, and 7.0. Dose response curves were fit using non-linear regression analysis to calculate the EC50 and slope. The peak tension with {alpha},{beta}-methyleneATP was lower during pH 7.0 (1.37±0.09g) compared to pH 7.8 (1.90±0.12g). EC50 was highest with pH 7.4 (-5.38±0.18 log M {alpha},{beta}-methyleneATP) and lowest with pH 7.0 (-4.9±0.10 log M {alpha},{beta}-methyleneATP). The slopes of the dose response curves were not different. PPADS abolished contraction caused by the addition of {alpha},{beta}-methyleneATP (n=6). There was no effect of pH on phenylephrine dose response curves. These data indicate that the vasoconstrictor response to {alpha},{beta}-methylene ATP is sensitive to pH and that lower pH attenuates the response of P2X purinergic receptors.




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