title: Acidosis attenuates P2X purinergic vasoconstriction in skeletal muscle arteries.
abstract: Vasoconstriction via alpha(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 alpha,beta-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 EC(50) and slope. The peak tension with alpha,beta-methylene ATP was lower during pH 7.0 (1.37 +/- 0.09 g) compared with pH 7.8 (1.90 +/- 0.12 g). EC(50) was highest with pH 7.4 (-5.38 +/- 0.18 log M alpha,beta-methylene ATP) and lowest with pH 7.0 (-4.9 +/- 0.10 log M alpha,beta-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 alpha,beta-methylene ATP (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.
authors.affiliation: Department of Anesthesiology and Physiology, Medical College of Wisconsin, Milwaukee, WI , USA.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Kluess
authors.forename: John B
authors.initials: JB
authors.lastname: Buckwalter
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Hamann
authors.forename: Philip S
authors.initials: PS
authors.lastname: Clifford
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010656:Phenylephrine / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D010656:Phenylephrine; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate