Am. J. Respir. Crit. Care Med., Volume 163, Number 5, April 2001, 1241-1245

Dissociation of Pulmonary Vascular Remodeling and Right Ventricular Pressure in Tissue Angiotensin-converting Enzyme-deficient Mice Under Conditions of Chronic Alveolar Hypoxia

ROBERT J. van SUYLEN, WENDY M. AARTSEN, JOS F. M. SMITS, and MAT J. A. P. DAEMEN

Departments of Pathology and Pharmacology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

The present study was designed to characterize the role of tissue angiotensin-converting enzyme (ACE) on pulmonary vascular remodeling and its functional consequences in chronic hypoxia. On the basis of data obtained by pharmacological inhibition of ACE in rats we hypothesized that, under chronic hypoxic conditions, tissue ACE-deficient mice show less remodeling of pulmonary arterioles as compared with wild-type mice, but have equally increased right ventricular pressures. Wild-type and tissue ACE-deficient mice were exposed 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 hypoxia induced significant remodeling of pulmonary arterioles in tissue ACE-deficient mice. The percentage of completely muscularized arterioles was, however, 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 tissue ACE does not prevent the MRVP and right ventricular weight from increasing during chronic hypoxia in the mouse. Also, pulmonary vascular remodeling occurs in hypoxic tissue ACE-deficient mice, albeit to a lower level than in mice that do have an intact ACE gene.

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