Effect of pH Change on Vascular Smooth Muscle Contractility in Rat Superior Mesenteric Artery and Its Branches

Abstract

Background: Extracellular and intracellular pH (pH o and pH i ), which can be changed in various pathological conditions such as hypoxia, affects vascular contractility. To elucidate the mechanism to alter vascular contractility by pH, the effects of pH on reactivity to vasocontracting agents, intracellular Ca²? influx, and Ca²? sensitivity in vascular smooth muscle were examined. Material and Method: Isometric contractions in rat superior mesenteric arteries (SMA) were observed. Intracellular Ca²? concentration ([Ca²?] i ) was recorded by microfluorometer using Fura-2/acetoxylmethyl ester in muscle cells. pH o was increased from 7.4 to 7.8 or decreased to 6.9 or 6.4. pH i was decreased by applying NH₄? or propionic acid or modulated by changing pH o after increasing membrane permeability using β-escin. Result: Decreases in pH o from 7.4 to 6.9 or 6.4 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the right and significantly increased half maximal effective concentration (EC50) to NE or SE. Increase in pH o from 7.4 to 7.8 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the left and significantly reduced EC50 to NE or SE. NE increased [Ca²?] i in cultured smooth muscle cells from SMA and the increased [Ca²?] i was reduced by decreases in pH o . NE-induced contraction was inhibited by NH₄?, whereas the resting tension was increased by NH₄? or propionic acid. When the cell membrane of SMA was permeabilized using β-escin, SMA was contracted by increasing extracellular Ca²? concentration from 0 to 10μM and the magnitude of contraction was decreased by a decrease in pH o and vice versa. Conclusion: From these results, it can be concluded that a decrease in pH o might inhibit vascular contraction by reducing the reactivity of vascular smooth muscle to vasoactive agents, Ca²? influx and the sensitivity of vascular smooth muscle to Ca²?.