The Role of Endothelium and of Extracellular and Intracellular Acidosis for Hypercapnia Induced Inhibition of Tension of Isolated Rat Cerebral Arteries

Abstract

The importance of changes in extracellular and intracellular pH (pH₀ and pH_i) for hypercapnic vasodilation was evaluated in vitro. Segments of the middle cerebral artery of the rat were mounted in a myograph for isometric tension recording and in all studies basal tension and tension in the presence of arginine vasopressin (AVP) was measured. pH_i was determined by loading the smooth muscle cells with the fluorescent dye bis-carboxy-ethyl-carboxy fluorescein. Control solution was a physiological saline solution with 25 mM HC0 ^-₃ ¯ and 5% C0₂ in the bubbling air (pH 7.45–7.50). Induction of hypercapnic acidosis (10% C₂O) or normocapnic acidosis (15 mMHC0 ^-₃ ¯) reduced pH_i as well as pH₀ and both caused significant reduction in AVP induced tension as well as in basal tension. Selective reduction in pH_i, obtained by reducing [HCO ^-₃ ¯] to 9 mM and CO₂ to 2.5% caused significant reduction in tensions induced by 1 as well as 2 U/l of AVP and in basal tension. Selective reduction in pH_i obtained by increasing [HCO ^-₃ ¯] to 65 mM and C0₂ to 15% decreased AVP tension at 1 U/l but not at 2 U/l and was accompanied by an increase in basal tension. The same pattern in the tension development following selective pH₀ and pH_i reduction was found after removal of the endothelium whether 1 μM sodium nitroprusside was present or not. L-NNA significantly inhibited the relaxation of the AVP response induced by hypercapnic acidosis. Responses to selective reductions in pH₀ or pH_i) in the presence of L-NNA were, however, qualitatively similar to responses seen in solutions without L-NNA.