Context: Extracellular hydrogen ion concentration (pHo) is an important physiological regulator of vascular tone, maintained within 7.35–7.45 and any change in it leads to complex health problem including maintenance of normal blood pressure. Aims: This study aims to examine the altered function of Na+-K+ pump and inward rectifier potassium channels (Kir) channels in extracellular acidosis in goat superior mesenteric artery (GSMA). Subjects and Methods: Isolated GSMA rings were mounted in an automatic organ bath containing 20-ml modified Krebs–Henseleit solution at pH 7.4/6.8/6.0 and KCl-induced contraction was elicited either in the absence or presence of ouabain, barium (Ba2+), and combination of ouabain and Ba2+. Rings were dilated with potassium chloride either in the absence or presence of ouabain, Ba2+ and combination of ouabain and Ba2+ while maintaining at acidic pH. The responses were recorded isometrically by highly sensitive isometric force transducer connected to Powerlab and analyzed using LabChart 7.1.3 software. Statistical Analysis Used: Data were analyzed in GraphPad Prism 5 software. Results: K+ vasorelaxation response in K+-free solution precontracted rings the percent maximal response (93.57 ± 2.57%, 62.60 ± 3.56%, and 53.38 ± 5.41%) was decreased with decrease pHo (7.4, 6.8 and 6.0). Ouabain, Ba2+, and ouabain and Ba2+ inhibited the maximal vasorelaxation of potassium chloride (26.20 ± 3.48%, 17.39 ± 0.54%, 31.92 ± 1.10%) at pHo7.4, (42.74 ± 2.48%, 16.12 ± 3.49%, 22.32 ± 1.63%) at pHo6.8, and (53.87 ± 2.18%, 25.24 ± 2.90%, 39.71 ± 0.14%) at pHo6.0, respectively. Conclusions: Attenuated vasodilation in acidosis is due to reduced function or expression of ouabain-sensitive sodium–potassium ATPase (Na+-K+-ATPase) and Kir channels. In clinical acidosis, agents augmenting the activity of Na+-K+-ATPase and K+-Channel could improve hypertensive crisis.