Vasorelaxation of goat mesenteric artery is mediated by endothelial Na+-K+-ATPase

Abstract

Objective:To examine the role of Na+-K+-ATPase and K+ channels in mediating vasorelaxation in the superior mesenteric artery of Capra hircus.Materials and Methods:Goat superior mesenteric artery (GSMA) was cut into 1.5–2 mm circular rings and mounted in a thermostatically controlled (37°C ± 0.5°C) organ bath containing 20 ml of modified Krebs-Henseleit saline (MKHS) (pH 7.4), with continuous aeration under 1.5 g tension for 90 min. Endothelium-intact (ED+) or endothelium-denuded (ED−) GSMA ring was contracted with phenylephrine (PE) or 5-hydroxytryptamine (5-HT) (1 μM–0.1 mM) in the absence or presence of ouabain (0.1 μM). KCl (1 μM–10 mM) was added cumulatively to K+-free MKHS-pre-contracted (ED+/−) rings in the absence or presence of ouabain (0.1 μM) or barium (1 μM) or 4-aminopyridine (1 μM).Results:Ouabain did not alter the basal tone of the arterial ring. The contractile response induced by PE (Emax: 50.46 ± 2.68, pD2: 5.53 ± 0.04) and 5-HT (Emax: 30.86 ± 1.33, pD2: 6.17 ± 0.03) in ED+ ring was significantly (P < 0.001) augmented in ED− rings (PE: Emax: 93.30 ± 2.11, pD2: 6.41 ± 0.04; 5-HT: Emax: 95.07 ± 0.99, pD2: 6.27 ± 0.03). The contractile response induced by PE and 5-HT in ED+ or ED− rings in the presence of ouabain was almost identical with that of ED− rings. Vasorelaxation of KCl (Emax: 2.90 ± 1.14, pD2: 3.9 ± 0.03) was significantly attenuated in the presence of ouabain (Emax: 73.8 ± 5.16, pD2: 4.3 ± 0.04), Ba2+ (Emax: 16.34 ± 4.7, pD2: 3.22 ± 0.02), 4-AP (Emax: 18.16 ± 2.4, pD2: 3.68 ± 0.03), ouabain and Ba2+ (Emax: 70.09 ± 3.66, pD2: 4.41 ± 0.04), and ouabain and 4-AP (Emax: 66.98 ± 4.61, pD2: 4.13 ± 0.06).Conclusion:The vasorelaxation in GSMA is mediated by the endothelium-derived hyperpolarizing factor (EDHFs) such as ouabain-sensitive Na+-K+-ATPase, KIR and Kv channels.