Nitrendipine attenuates the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia in rats

Abstract

We designed experiments to determine whether intermittent hypoxia would produce significant pathologic and physiologic changes in rats and whether pretreatment with a calcium channel blocker, nitrendipine, would reduce the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia. Intermittent exposure to hypobaric hypoxia (0.5 atmospheres) 10 h a day for 30 days increased the hematocrit (65 +/- 1 versus 42 +/- 1%, mean +/- SEM), right ventricular systolic pressure (33 +/- 1 versus 20 +/- 1 mmHg), and right ventricular weight adjusted for body weight (RV/BW) (126 +/- 6 versus 60 +/- 2 mg/100 g) in male Sprague-Dawley rats. Intermittent hypoxia also increased the percentage of small pulmonary vessels with muscle (76 +/- 3 versus 19 +/- 5%) and the thickness of the vessel wall as a percentage of the total vessel diameter (34 +/- 1 versus 22 +/- 1%). Nitrendipine (10 mg/kg) prevented the acute increase in right ventricular systolic pressure caused by hypoxia. Chronic treatment with nitrendipine (10 mg/kg given twice a day by gavage for 30 days) significantly reduced the increase in hematocrit (61 +/- 1 versus 65 +/- 1%), right ventricular systolic pressure (29 +/- 1 versus 33 +/- 1 mmHg), and RV/BW (108 +/- 4 versus 126 +/- 6 mg/100 g) caused by hypoxia. Chronic treatment with nitrendipine also reduced the percentage of small pulmonary vessels with muscle (38 +/- 8 versus 76 +/- 3%) and prevented the increase in vessel wall thickness (20 +/- 2 versus 34 +/- 1%). Thus, nitrendipine treatment significantly reduces the right ventricular hypertrophy and pulmonary vascular changes caused by intermittent hypoxia.