Regional heterogeneity in acetylcholine-induced relaxation in rat vascular bed: Role of calcium-activated K⁺ channels

Ca⁺-activated K⁺-channels (K_Ca) regulate vasomotor tone via smooth muscle hyperpolarization and relaxation. The relative contribution of the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation differs depending on vessel type and size. It is unknown whether these K_Ca channels are differentially distributed along the same vascular bed and hence have different roles in mediating the EDHF response. We therefore assessed the role of small- (SK_Ca), intermediate- (IK _Ca), and large-conductance (BK_Ca) channels in mediating acetylcholine-induced relaxations in both first- and fourth-order side branches of the rat superior mesenteric artery (MA1 and MA4, respectively). Two-millimeter segments of each MA were mounted in the wire myograph, incubated with N^ω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/l) and indomethacin (10 μmol/l), and precontracted with phenylephrine (10 μmol/l). Cumulative concentration-response curves to ACh (0.001-10 μmol/l) were performed in the absence or presence of selective K_Ca channel antagonists. Apamin almost completely abolished these relaxations in MA4 but only partially blocked relaxations in MA1. The selective IK_Ca channel blocker 1-[(2chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) caused a significantly greater inhibition of the ACh-induced relaxation in MA4 compared with MA1. Iberiotoxin had no inhibitory effect in MA4 but blunted relaxation in MA1. Relative mRNA expression levels of SK_Ca (rSK1, rSK3, and rSK4 = rIK1) were significantly higher in MA4 compared with MA1. BK_Ca (rBKα₁ and rBKβ₁) genes were similar in both MA1 and MA4. Our data demonstrate regional heterogeneity in SK_Ca and IK_Ca function and gene expression and stress the importance of these channels in smaller resistance-sized arteries, where the role of EDHF is more pronounced.