Acid stress reduces the function of Na+-K+-ATPase in superior mesenteric artery of Capra hircus

Abstract

Context: Extracellular hydrogen ion concentration (pH o ) 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 (K ir ) 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 (Ba 2+ ), and combination of ouabain and Ba 2+ . Rings were dilated with potassium chloride either in the absence or presence of ouabain, Ba 2+ and combination of ouabain and Ba 2+ 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 pH o (7.4, 6.8 and 6.0). Ouabain, Ba 2+ , and ouabain and Ba 2+ inhibited the maximal vasorelaxation of potassium chloride (26.20 ± 3.48%, 17.39 ± 0.54%, 31.92 ± 1.10%) at pH o 7.4, (42.74 ± 2.48%, 16.12 ± 3.49%, 22.32 ± 1.63%) at pH o 6.8, and (53.87 ± 2.18%, 25.24 ± 2.90%, 39.71 ± 0.14%) at pH o 6.0, respectively. Conclusions: Attenuated vasodilation in acidosis is due to reduced function or expression of ouabain-sensitive sodium–potassium ATPase (Na + -K + -ATPase) and K ir channels. In clinical acidosis, agents augmenting the activity of Na + -K + -ATPase and K + -Channel could improve hypertensive crisis. Abbreviations used: Ba 2+ : Barium; E max : Percent maximal response; E Bmax : Percent maximal response in presence of antagonist; K ATP : Adenosine triphosphate-sensitive potassium channel; K ir : Inward rectifier potassium channels; K Ca : Calcium-activated potassium channels; Na + -K + -ATPase: Sodium–potassium ATPase; NO: Nitric oxide; pH i : Intracellular hydrogen ion concentration; pH o : Extracellular hydrogen ion concentration; VSMCs: Vascular smooth muscle cells.