Comparative effects of nisoldipine, nifedipine and bepridil on experimental pulmonary hypertension

Calcium channel blockers sometimes reduce pulmonary vascular resistance (PVR) in patients with pulmonary hypertension. This study compares the pulmonary vasodilator effect of two new calcium channel blockers, nisoldipine and bepridil, to that of nifedipine in 3 groups of anesthetized dogs (n = 8 for each group). In each group the normoxic hemodynamics were recorded before and after low, medium and high doses of the respective agents given i.v. In addition, the effect of these doses on the pulmonary pressor responses to hypoxia and prostaglandin F(2α) (PGF(2α)) was measured. During normoxia all doses of bepridil caused brief increases in cardiac output. However, during the hypoxic and PGF(2α) challenges cardiac output fell and PVR rose above predrug responses, rather than being reduced. Nisoldipine produced a sustained increase in cardiac output throughout the experiment. During hypoxia, at high dose, it decreased pulmonary arterial pressure, unlike the 2 other agents. However, in common with them, nisoldipine also caused systemic hypotension. After medium and high dose nisoldipine and after high dose nifedipine, PVR remained close to normoxic control levels during both hypoxic and PGF(2α) challenges. Both medium dose nisoldipine (5 x 10^-8 M/kg) and high dose nifedipine (5 x 10^-7 M/kg) reduced hypoxic PVR by 39% of the untreated hypoxic value. Although nisoldipine is more effective in reducing pulmonary hypertension than nifedipine or bepridil, it also causes marked systemic hypotension. This lack of specificity may limit the therapeutic potential of this agent when given i.v.