Dissociation of pulmonary vascular remodeling and right ventricular pressure in tissue angiotensin-converting enzyme-deficient mice under conditions of chronic alveolar hypoxia

The present study was designed to characterize the role of tissue angiotens in-converting enzyme (ACE) on pulmonary vascular remodeling and its functio nal consequences in chronic hypoxia. On the basis of data obtained by pharm acological inhibition of ACE in rats we hypothesized that, under chronic hy poxic conditions, tissue ACE-deficient mice show less remodeling of pulmona ry arterioles as compared with wild-type mice, but have equally increased r ight ventricular pressures. Wild-type and tissue ACE-deficient mice were ex posed to chronic hypoxia for 4 wk. Absence of tissue ACE did not affect the increase in the mean right ventricular pressures (MRVP) and the extent of right ventricular hypertrophy under chronic hypoxic conditions. Chronic hyp oxia induced significant remodeling of pulmonary arterioles in tissue ACE-d eficient mice. The percentage of completely muscularized arterioles was, ho wever, lower in tissue ACE-deficient mice compared with wild-type animals ( 29 +/- 12 versus 41 +/- 18%, p < 0.05), whereas the percentage of partially muscularized arterioles had increased (48 +/- 11 versus 39 +/- 11%, p < 0. 05). No sex-based effects were found. We conclude that the absence of tissu e ACE does not prevent the MRVP and right ventricular weight from increasin g during chronic hypoxia in the mouse. Also, pulmonary vascular remodeling occurs in hypoxic tissue ACE-deficient mice, albeit to a lower level than i n mice that do have an intact ACE gene.