EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITOR AND CALCIUM CHANNEL BLOCKER ON NORMOXIC AND HYPOXIC PULMONARY VASCULAR TONE IN UNANESTHETIZED SHEEP

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We evaluated the effects of captopril and nifedipine on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep. Infusion of captopril (10 μg/kg/min) in normoxia revealed a tendency to increase the mean pulmonary arterial pressure (Ppa) and the pulmonary vascular resistance (PVR) following the systemic vasocilation. A statistically significant increase was reached by 20 minutes. Hypoxia of 10% oxygen in nitrogen produced a prominent pulmonary hypertensive response. Captopril significantly decreased the hypoxic values of Ppa and PVR from 20.3±1.3 to 17.1±1.1 mmHg (p<0.01) and from 4.31±0.45 to 3.49±0.45 mmHg/L/min (p<0.01), respectively. Infusion of nifedipine (10 μg/kg/min) in normoxia caused an increase in Ppa from 15.5±0.9 to 18.9±1.0 mmHg (p<0.01), but not in PVR. This elevation in Ppa was considered to be derived from the significant increase in the cardiac output. Nifedipine significantly decreased the hypoxic values of Ppa and PVR from 21.3±1.5 to 19.3±1.5 mmHg (p<0.01), respectively. Captopril and nifedipine produced systemic hypotensive responses during both normoxic and hypoxic ventilation. It is concluded that both captopril and nifedipine are potent pulmonary vasodilating drugs in animal subjects with a hypoxic condition and that they might be useful in the clinical vasodilator therapy of hypoxic pulmonary hypertension in man.