Nitrendipine Reduces Acute and Chronic Hypoxic Pulmonary Hypertension in Rats

Abstract

We investigated the effects of nitrendipine, a calcium channel blocker with a reportedly long duration of action, on the pulmonary vascular responses to acute and chronic hypoxia. Studies were performed in the catheterized conscious rat with established hypoxic pulmonary hypertension to assess whether nitrendipine might be a useful drug for the treatment of pulmonary hypertension. Nitrendipine dose-response curves showed that 10 mg/kg i.p. and 15 mg/kg s.c. inhibited the hypoxic pressor response by 50% or more for at least 4h. Nitrendipine (10 mg/kg i.p.) also produced significant systemic hypotension. Nitrendipine, given chronically (1–30 mg/kg/day) to rats exposed to chronic intermittent hypoxia, had no effect on pulmonary arterial pressure or total pulmonary resistance, as measured while the rats were breathing room air. However, at doses of 3 mg/kg/day and greater, nitrendipine produced a decrease in vascular reactivity to acute hypoxia. At 10 and 30 mg/kg/day, nitrendipine decreased the development of right ventricular and pulmonary vascular hypertrophy. It made no difference whether each dose was given as a single administration or as multiple doses. We conclude that nitrendipine inhibits acute hypoxic pulmonary vasoconstriction and reduces established hypoxic pulmonary hypertension in the rat.