Contribution of Na⁺-K⁺ pump and K_IR currents to extracellular pH-dependent changes of contractility in rat superior mesenteric artery

We compared the branches and trunk of rat superior mesenteric artery (SMA) with respect to extracellular pH (pH_o)-dependent changes in vascular contractility. Decreases in pH_o from 7.8 to 6.4 significantly reduced apparent affinity (pD₂) to norepinephrine (NE) and maximal contraction by NE, which were more prominent in larger-diameter arteries. On the other hand, decreases in pH_o significantly reduced Ba ²⁺-sensitive K⁺-induced relaxation (which was evoked by elevation of extracellular K⁺ concentration from 6 to 12 mM) in the first branch and inhibited inwardly rectifying K⁺ (K_IR) currents in cultured smooth muscle cells (SMCs) of SMA. RT-PCR revealed transcripts for Kir2.1 in the SMCs. Real-time PCR analysis revealed 6.1-, 3.3-, and 2.2-fold increases in the Kir2.1 mRNA-to-β-actin mRNA ratios of SMCs of the third, second, and first branches, respectively, vs. the corresponding relative levels of trunk SMCs. The magnitudes of K⁺-induced relaxation were significantly greater in smaller-diameter arteries, and there was a strong correlation between the transcript levels of Kir2.1 and K ⁺-induced relaxation. A decrease in pH_o reduced ouabain-sensitive K⁺-induced relaxation and ouabain-induced contraction. A decrease in pH_o from 7.4 to 6.4 depolarized membrane potential of the cultured SMCs. From these results, we conclude that an increase in pH_o activates K_IR currents and the Na ⁺-K⁺ pump, which then reduces vascular contractility. Inasmuch as KIR channel densities are significantly greater in smaller-diameter arteries, the reduction in vascular contractility on increasing pH_o is more pronounced in smaller-diameter arteries.