ACE inhibitors in HF restore canine pulmonary endothelial function and ANGII vasoconstriction

Chronic mitral regurgitation (MR) in dogs results in pulmonary congestion a nd increased cardiac angiotensin-converting enzyme (ACE) activity and angio tensin (ANG) II levels. ACE could contribute to altered pulmonary vasomotio n in heart failure, and ACE inhibitor (ACEI) therapy may normalize pulmonar y vasomotion. We evaluated pulmonary artery (PA) responses to ANG II and br adykinin (BK) in control dogs, in dogs with 4 mo of MR, in MR dogs treated with the ACEI ramipril (MR + R), and in control dogs treated with ramipril( C + R). Mean PA systolic pressure increased in MR dogs (21 +/- 4 mmHg) but was normal in MR + R dogs (13 +/- 1 mmHg). Constriction of PA rings to ANG II was depressed in MR dogs. ACEI treatment (MR + R) restored ANG II respon siveness, but peak ANG II response (3.6 +/- 0.2 g) in MR + R dogs remained lower than in C + R dogs (4.7 +/- 0.2 g). Endothelium-dependent relaxation to BK was decreased (-87 +/- 4% C, -65 +/- 4% MR; P < 0.05). Ramipril (MR R) restored relaxation to BK. This demonstrates that pulmonary congestion results in impaired pulmonary vasomotion to ANG; II and BK, which ACEIs cou ld normalize, supporting the use of ACEIs in clinical management of chronic congestive heart failure.