Effect of a decrease in pH on responses mediated by P2 receptors in the rat mesenteric arterial bed.
The present study investigated the effect of acidosis (reduction in pH of the Krebs' solution from 7.4 to 6.9) on responses to vasoconstrictors and vasodilators, with a focus on purines, in the rat isolated perfused mesenteric arterial bed. alpha,beta-Methylene ATP (alpha,beta-meATP) (10 microM), a selective P2X receptor agonist, elicited a desensitizing vasocontraction, which was not significantly affected by a reduction in pH to 6.9. Contractions to ATP were also not significantly different at pH 6.9 compared to pH 7.4. In contrast, contractile responses to noradrenaline, methoxamine, and vasopressin were greatly attenuated at pH 6.9 (by 48-83%; P<0.01). At raised tone, vasorelaxations to ADP at P2Y receptors, and to calcitonin gene-related peptide (CGRP), were not different at pH 7.4 and pH 6.9. These data indicate that a reduction in pH (to 6.9) differentially affects responses to vasoconstrictors in the rat mesenteric arterial bed. There is no effect on contractions mediated via P2X receptors, but contractions to noradrenaline, methoxamine and vasopressin are greatly attenuated.
Ralevic
V
V
School of Biomedical Sciences, Queen's Medical Centre, The University of Nottingham, NG7 2UH, Nottingham, UK. vera.ralevic@nottingham.ac.uk
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D018048:Receptors, Purinergic P2; D014667:Vasopressins; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D008729:Methoxamine; D015740:Calcitonin Gene-Related Peptide; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine