ANGIOTENSIN-CONVERTING ENZYME EXPRESSION IS INCREASED IN SMALL PULMONARY-ARTERIES OF RATS WITH HYPOXIA-INDUCED PULMONARY-HYPERTENSION

Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE a ttenuate hypoxic pulmonary hypertension, In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression, The experimen tal approach combined in vivo hemodynamic studies in control and chron ically hypoxic rats, measurement of whole lung ACE activity, and evalu ation of local pulmonary vascular ACE expression by in situ hybridizat ion and immunohistochemistry. Total lung ACE activity was reduced to 5 0% of control activity by 5 d of hypoxia and remained low for the dura tion of the study, Immunohistochemistry showed a marked reduction of A CE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pu lmonary arteries at the level of alveolar ducts and walls. In situ hyb ridization studies showed increased signal for ACE mRNA in the same ve ssels. Inhibition of ACE by captopril during chronic hypoxia attenuate d pulmonary hypertension and markedly reduced distal muscularization o f small pulmonary arteries, In addition, we demonstrated marked longit udinal variation in ACE expression along the normal pulmonary vasculat ure with the highest levels found in small muscular arteries associate d with terminal and respiratory bronchioles, We conclude that local AC E expression is increased in the walls of small pulmonary arteries dur ing the development of hypoxic pulmonary hypertension, despite a gener alized reduction in alveolar capillary ACE expression, and we speculat e that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.