title: 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.
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology; D006984:Hypertrophy; D000860:Hypoxia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009568:Nitrendipine; D009543:Nifedipine