Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs

Abstract

Acute hypoxia increases pulmonary arterial pressure and vascular resistance. Previous studies in isolated smooth muscle and perfused lungs have shown that carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic pulmonary vasoconstriction (HPV). We studied whether CA inhibition by acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten chronically tracheotomized, conscious dogs were investigated in three protocols. In all protocols, the dogs breathed 21% O2for the first hour and then 8 or 10% O2for the next 4 h spontaneously via a ventilator circuit. The protocols were as follows: protocol 1: controls given no Acz, inspired O2fraction (FiO2) = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167 μg·kg−1·min−1continuously), FiO2= 0.10; protocol 3: Acz given as above, but with FiO2reduced to 0.08 to match the arterial Po2(PaO2) observed during hypoxia in controls. PaO2was 37 Torr during hypoxia in controls, mean pulmonary arterial pressure increased from 17 ± 1 to 23 ± 1 mmHg, and pulmonary vascular resistance increased from 464 ± 26 to 679 ± 40 dyn·s−1·cm−5( P < 0.05). In both Acz groups, mean pulmonary arterial pressure was 15 ± 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440 dyn·s−1·cm−5. These values did not change during hypoxia. In dogs given Acz at 10% O2, the arterial PaO2was 50 Torr owing to hyperventilation, whereas in those breathing 8% O2the PaO2was 37 Torr, equivalent to controls. In conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The effect is not due to Acz-induced hyperventilation and higher alveolar Po2, nor to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV suppression occurs despite the systemic acidosis with CA inhibition.