Differential contractile effects of changes in carbon dioxide tension on rat mesenteric resistance arteries precontracted with noradrenaline

Abstract

The pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF) was used to measure intracellular pH (pHi) in rat mesenteric resistance arteries (internal diameter 152-289 microns) mounted in an isometric myograph for simultaneous measurements of force. Extracellular pH was measured using a pH-sensitive electrode. Experiments were designed to test contractile electrode. Experiments were designed to test contractile effects of changes in carbon dioxide tension (PCO2) on vessels precontracted with noradrenaline. An acute increase in PCO2 caused acute intracellular acidification and potentiation of contractility. The longer-term effect, however, was recovery of intracellular pH and vaso-relaxation. Opposite changes in tension and intracellular pH were observed by decreasing PCO2. Qualitatively similar changes in contractility were observed in response to changes in pHi induced by NH4Cl. Thus, effects on vessels precontracted with noradrenaline were biphasic. In another set of experiments, the amplitude of the transient responses to 50 microM noradrenaline in calcium-free media was significantly augmented by an increase in the PCO2, whereas the response to 5 microM noradrenaline 1 min after readdition of calcium to the medium was depressed by the rise in PCO2. These data suggest that acute intracellular acidification causes acute tension development and are consistent with the possibility that the biphasic response to changes in noradrenaline-induced contractility caused by changes in PCO2 may be ascribed to differential effects on calcium mobilisation processes.