Augmented sympathoinhibitory effect of valsartan when added to angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction

• Published in: Journal of cardiology Vol. 53; no. 2; pp. 171 - 178
• Main Authors: Kawamura, Akihiro, MD, Yuasa, Fumio, MD, Yokoe, Hiroshi, MD, Masue, Yoh, MD, Sugiura, Tetsuro, MD, FJCC, Iwasaka, Toshiji, MD, FJCC
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2009
• Subjects: Angiotensin Receptor Antagonists - administration & dosage; Angiotensin Receptor Antagonists - pharmacology; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Arterial baroreflex sensitivity; Arteries - drug effects; Baroreflex - drug effects; Cardiopulmonary baroreflex sensitivity; Cardiovascular; Drug Synergism; Enalapril - administration & dosage; Enalapril - pharmacology; Female; Heart - drug effects; Hemodynamics - drug effects; Humans; Lung - drug effects; Male; Middle Aged; Sympathetic nerve activity; Sympathetic Nervous System - drug effects; Tetrazoles - administration & dosage; Tetrazoles - pharmacology; Valine - administration & dosage; Valine - analogs & derivatives; Valine - pharmacology; Valsartan; Ventricular Dysfunction, Left - drug therapy; Arterial baroreflex sensitivity; Cardiopulmonary baroreflex sensitivity; Sympathetic nerve activity
• ISSN: 0914-5087; 1876-4738
• DOI: 10.1016/j.jjcc.2008.09.016

Summary Objective Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the sympathetic nerve activity in patients with left ventricular (LV) dysfunction. The aim of this study was to examine the effect of ARBs on sympathetic nerve activity and baroreflex function in patients with LV dysfunction already receiving ACE inhibitors. Methods Twenty patients with LV dysfunction already treated with ACE inhibitor (enalapril 5 mg/day) were randomly divided into two groups: treatment with 10 mg/day enalapril (control group) or 5 mg/day enalapril plus 80 mg/day valsartan (combination group). In both groups, resting muscle sympathetic nerve activity (MSNA; microneurography), arterial baroreflex sensitivity, and cardiopulmonary baroreflex sensitivity were measured at baseline and 4 weeks after the treatment. Arterial baroreflexes were perturbed by phenylephrine method, and cardiopulmonary baroreflexes were perturbed by lower body negative pressure (−10 mmHg). Results Baseline characteristics in both groups were similar. Resting MSNA decreased significantly from 35.4 ± 10.8 to 26.4 ± 5.1 burst/min ( p < 0.05), while arterial baroreflex sensitivity improved significantly from 6.0 ± 2.0 to 10.1 ± 2.6 ms/mmHg in the combination group. Moreover, cardiopulmonary baroreflex control of MSNA improved significantly from 15.8 ± 12.2 to 42.0 ± 26.7% ( p < 0.05) in the combination group. However, there were no significant changes in arterial baroreflex sensitivity and cardiopulmonary baroreflex of MSNA in the control group. Conclusion Addition of ARB to ACE inhibitor treatment reduced sympathetic nerve activity and augmented arterial and cardiopulmonary baroreflex sensitivity in patients with LV dysfunction.