Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure.

Abstract

Chronic angiotensin-converting enzyme (ACE) inhibition has been shown to improve cardiac sympathetic nerve terminal function in heart failure. To determine whether similar effects could be produced by angiotensin II AT(1) receptor blockade, we administered the ACE inhibitor quinapril, angiotensin II AT(1) receptor blocker losartan, or both agents together, to rabbits with pacing-induced heart failure. Chronic rapid pacing produced left ventricular dilation and decline of fractional shortening, increased plasma norepinephrine (NE), and caused reductions of myocardial NE uptake activity, NE histofluorescence profile, and tyrosine hydroxylase immunostained profile. Administration of quinapril or losartan retarded the progression of left ventricular dysfunction and attenuated cardiac sympathetic nerve terminal abnormalities in heart failure. Quinapril and losartan together produced greater effects than either agent alone. The effect of renin-angiotensin system inhibition on improvement of left ventricular function and remodeling, however, was not sustained. Our results suggest that the effects of ACE inhibitors are mediated via the reduction of angiotensin II and that angiotensin II plays a pivotal role in modulating cardiac sympathetic nerve terminal function during development of heart failure. The combined effect of ACE inhibition and angiotensin II AT(1) receptor blockade on cardiac sympathetic nerve terminal dysfunction may contribute to the beneficial effects on cardiac function in heart failure.

• Authors: H Kawai, S Y Stevens, C S Liang
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 279 Issue 6 Pg. H3012-9 (Dec 2000) ISSN: 0363-6135 [Print] United States
• PMID: 11087259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Isoquinolines
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin
• Tetrahydroisoquinolines
• Tyrosine 3-Monooxygenase
• Losartan
• Quinapril
• Norepinephrine

Topics

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Fluorescent Antibody Technique
• Heart (innervation, physiology)
• Heart Failure (drug therapy, physiopathology)
• Hemodynamics (drug effects, physiology)
• Isoquinolines (pharmacology)
• Losartan (pharmacology)
• Neurons (chemistry, enzymology)
• Norepinephrine (analysis, blood)
• Pacemaker, Artificial
• Presynaptic Terminals (metabolism)
• Quinapril
• Rabbits
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin (metabolism)
• Renin-Angiotensin System (drug effects, physiology)
• Tetrahydroisoquinolines
• Tyrosine 3-Monooxygenase (metabolism)
• Ventricular Function, Left (physiology)