INTRACORONARY BLOCKADE OF ANGIOTENSIN-CONVERTING ENZYME IN HUMANS - INTERACTION WITH CARDIAC SYMPATHETIC NEUROTRANSMISSION

The present study was designed to identify an interaction between the renin-angiotensin system and noradrenergic transmission in the human h eart. It is still under debate whether angiotensin ii facilitates nora drenaline release in the heart. Clinical studies of congestive heart f ailure, involving systemic angiotensin-converting enzyme (ACE) inhibit or administration, have indicated anti-adrenergic effects, without giv ing a clear mechanistic picture. The influence on cardiac sympathetic transmission by local intracardiac administration of an ACE inhibitor has not been determined. Seven angina patients with normal left ventri cular function, who underwent control coronary angiography after succe ssful percutaneous transluminal coronary angioplasty were studied. Bas eline measurements of haemodynamics and total and cardiac noradrenalin e spillover were followed by handgrip exercise in the absence and pres ence of intracoronary enalaprilat infusion (0.05 mg min(-1), 1 mL min( -1)). Baseline total body and cardiac noradrenaline spillover remained unchanged following intracoronary enalaprilat infusion, being 3745 +/ - 349 and 3896 +/- 257 pmol min(-1), and 148 +/- 56 and 149 +/- 55 pmo l min(-1), before and after drug administration, respectively. Mean ar terial pressure, peripheral plasma renin activity and angiotensin II l evels were also unaffected by enalaprilat infusion. During handgrip ex ercise procedures, both total body and cardiac noradrenaline spillover increased substantially, showing no reduction in the presence of intr acardiac enalaprilat. Direct administration of the ACE inhibitor enala prilat to the human heart failed to attenuate cardiac sympathetic driv e during baseline conditions or following cardiac adrenergic activatio n by handgrip exercise. Thus, in the non-failing heart, without chroni c adrenergic activation, no angiotensin II-facilitated effect on cardi ac noradrenaline spillover could be detected.