Prevention and reversal of hypoxic pulmonary hypertension by calcium antagonists

Abstract

There exists no agreement as to the best vasodilator drug for treatment of hypoxic pulmonary hypertension. We wondered which of 3 commonly used vasodilators - verapamil, nifedipine, or hydralazine - would be the most effective in reducing and reversing the development of hypoxic pulmonary hypertension in the conscious rat. Hemodynamic studies showed that all 3 drugs inhibited the pressor response to acute hypoxia. Given for 1 month to conscious rats during exposure to intermittent hypoxia, verapamil and nifedipine reduced pulmonary hypertension when compared with hypoxic control animals, as indicated by right ventricular hypertrophy, total pulmonary resistance, and medial thickening. Hydralazine caused similar, but smaller, changes. Nifedipine, when used to reverse established hypoxic pulmonary hypertension, reduced right ventricular hypertrophy and medial thickening. Cardiac and systemic effects were negligible. These results demonstrate that the calcium channel blockers reduce the development of hypoxic pulmonary hypertension and that nifedipine partially reverses established hypertension.