ACE inhibition improves cardiac NE uptake and attenuates sympathetic nerveterminal abnormalities in heart failure

Cardiac sympathetic nerve terminal dysfunction plays an important role in t he downregulation of myocardial beta-adrenoceptors in heart failure. To det ermine whether chronic angiotensin-converting enzyme (ACE) inhibition impro ved cardiac sympathetic nerve terminal function and hence increased myocard ial beta-adrenergic responsiveness, we administered ACE inhibitors to dogs with chronic right-sided heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. The RHF animals exhibited fluid retenti on, elevated right heart filling pressures, blunted inotropic response to i soproterenol, and reduced beta-adrenoceptor density. These changes were acc ompanied by decreases in right ventricular norepinephrine (NE) uptake and n euronal NE histofluorescence and tyrosine hydroxylase immunoreactive profil es. ACE inhibitors had no effect on the production of heart failure but gre atly reduced the attenuation of cardiac NE uptake, neuronal NE histofluores cence, and tyrosine hydroxylase immunoreactive profiles. ACE inhibition als o improved the inotropic response to isoproterenol and restored myocardial beta-adrenoceptor density. The changes probably are caused by reduction of cardiac NE release by ACE inhibition and may contribute to the beneficial e ffects of ACE inhibitor therapy in patients with chronic heart failure.