title: Intracoronary blockade of angiotensin-converting enzyme in humans: interaction with cardiac sympathetic neurotransmission?
abstract: The present study was designed to identify an interaction between the renin-angiotensin system and noradrenergic transmission in the human heart. It is still under debate whether angiotensin II facilitates noradrenaline release in the heart. Clinical studies of congestive heart failure, involving systemic angiotensin-converting enzyme (ACE) inhibitor administration, have indicated anti-adrenergic effects, without giving 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 ventricular function, who underwent control coronary angiography after successful percutaneous transluminal coronary angioplasty were studied. Baseline measurements of haemodynamics and total and cardiac noradrenaline spillover were followed by handgrip exercise in the absence and presence 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 pmol min-1, before and after drug administration, respectively. Mean arterial pressure, peripheral plasma renin activity and angiotensin II levels were also unaffected by enalaprilat infusion. During handgrip exercise procedures, both total body and cardiac noradrenaline spillover increased substantially, showing no reduction in the presence of intracardiac enalaprilat. Direct administration of the ACE inhibitor enalaprilat to the human heart failed to attenuate cardiac sympathetic drive during baseline conditions or following cardiac adrenergic activation by handgrip exercise. Thus, in the non-failing heart, without chronic adrenergic activation, no angiotensin II-facilitated effect on cardiac noradrenaline spillover could be detected.
authors.affiliation: Department of Cardiology, Heart and Lung Institute, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Rundqvist
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: H
authors.initials: H
authors.lastname: Emanuelsson
authors.forename: P
authors.initials: P
authors.lastname: Albertsson
authors.forename: P
authors.initials: P
authors.lastname: Friberg
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood; D015773:Enalaprilat / Q000008:administration & dosage* / Q000097:blood; D018737:Hand Strength; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007537:Isometric Contraction; D007700:Kinetics; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood; D012083:Renin / Q000097:blood / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013566:Sympathomimetics / Q000008:administration & dosage / Q000097:blood; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014316:Tritium
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013566:Sympathomimetics; D014316:Tritium; D000804:Angiotensin II; D012083:Renin; D015773:Enalaprilat; D009638:Norepinephrine