Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Effect of hypocapnia on extracellular glutamate and glycine concentrations during peri-ischemic period in the rabbit hippocampus

Glutamate (GLU) is a neurotransmitter. Massive release of GLU and glycine (GLY) into the brain's extracellular space may be triggered by ischemia, and may result in acute neuronal lysis or delayed neuronal death. The aim of this study was to evaluate the possible relationship between hyperventilation and the level of GLU and GLY during brain ischemia. Rabbits were anesthetized with halothane and oxygen. Group 1 was allowed to hyperventilate (PaCO2 25-35 mmHg). PaCO2 was maintained throughout the study. Group 2 was a normal control group that maintained normocapnia. Two global cerebral ischemic episodes were produced. Microdialysate was collected during the peri-ischemic and reperfusion periods from the dorsal hippocampus. GLU and GLY concentrations were determined using high-performance liquid chromatography. In the control group, GLU and GLY were significantly elevated during each episode of ischemia; these levels returned to baseline within 10 minutes after reperfusion. In contrast, in the hyperventilation group GLU and GLY concentrations increased during ischemia, but they were not statistically significant. We were able to demonstrate that hypocapnia during periischemic period lowered extracellular GLU and GLY concentrations. These results can explain a part of the protective action of hypocapnia during cerebral ischemia.