Abstract
Background: We recently reported that Ren‐2 rats, which express the mouse renin gene in extra‐renal tissues leading to local Ang II formation and hypertension, exhibit pulmonary hypertension (PH) and remodeling small pulmonary arteries. Here we test the hypothesis that PH and pulmonary vascular remodeling in the Ren‐2 rat is modulated by intrapulmonary oxidative stress.Methods: 6 week old Ren‐2 and Sprague Dawley (SD) rats were treated with tempol (superoxide scavenger) or vehicle for 3 weeks. Right ventricular systolic pressure (RVSP), wall thickness of small pulmonary arteries (PA), intrapulmonary NADPH oxidase activity and reactive oxygen species (ROS) were compared.Results: RVSP was higher in Ren2 compared to SD (61±7 mmHg vs 36±1; p<0.01); RVSP of tempol treated Ren2 (43±6 mmHg) was not different from untreated SD. Compared to SD, medial surface area of PA was 38% greater (p<0.001) and luminal surface area was 54% less (p<0.001) in Ren2; tempol treatment prevented these changes (p<0.05). ROS and NADPH oxidase activity were elevated in Ren2 lungs compared to SD (p<0.05) and tempol treatment prevented these increases (p<0.05).Conclusions: Ren2 rats exhibit intrapulmonary oxidative stress, medial thickening of PA, and PH, and tempol treatment ameliorates these changes. This study supports a role for enhanced tissue RAS/oxidative stress as factors in development of PH and pulmonary vascular remodeling.
Published Version
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