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Effect of a decrease in pH on responses mediated by P2 receptors in the rat mesenteric arterial bed
1School of Biomedical Sciences, Queen's Medical Centre, The University of Nottingham, NG7 2UH, Nottingham, UK. vera.ralevic@nottingham.ac.uk
European Journal of Pharmacology
|September 30, 2000
Summary
Acidosis (lower pH) significantly reduces vasoconstrictor responses to noradrenaline, methoxamine, and vasopressin in rat mesenteric arteries. However, purinergic vasoconstrictor responses via P2X receptors remain unaffected by acidosis.
Area of Science:
- Physiology
- Pharmacology
- Cardiovascular Research
Background:
- Acidosis, a common physiological condition, can alter vascular reactivity.
- Understanding how pH changes affect blood vessel responses is crucial for managing various diseases.
Purpose of the Study:
- To investigate the impact of acidosis on vasoconstrictor and vasodilator responses in the rat isolated perfused mesenteric arterial bed.
- To determine the specific effects of reduced pH on purinergic signaling pathways.
Main Methods:
- Utilized a rat isolated perfused mesenteric arterial bed model.
- Administered vasoconstrictors (alpha,beta-methylene ATP, ATP, noradrenaline, methoxamine, vasopressin) and vasodilators (ADP, CGRP) at normal (pH 7.4) and acidic (pH 6.9) conditions.
- Quantified changes in vascular tone and contractile/relaxant responses.
Main Results:
- Acidosis (pH 6.9) significantly attenuated contractile responses to noradrenaline, methoxamine, and vasopressin (48-83% reduction).
- Contractions induced by alpha,beta-methylene ATP and ATP (acting on P2X receptors) were not significantly affected by acidosis.
- Vasorelaxations to ADP (P2Y receptors) and CGRP were unchanged under acidic conditions.
Conclusions:
- Reduced pH differentially affects vasoconstrictor responses in the rat mesenteric arterial bed.
- P2X receptor-mediated contractions are resistant to acidosis, while responses to other vasoconstrictors are significantly impaired.
- These findings highlight the complex interplay between pH and vascular smooth muscle function.