This Article Full Text Full Text (PDF) All Versions of this Article: 108/2/225    most recent 01.CIR.0000079226.48637.5Av1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tallaj, J. Articles by Dell’Italia, L. J. Search for Related Content PubMed PubMed Citation Articles by Tallaj, J. Articles by Dell’Italia, L. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB EPINEPHRINE METOPROLOL Related Collections Congestive Heart failure - basic studies

(Circulation. 2003;108:225.)
© 2003 American Heart Association, Inc.

Basic Science Reports

ß₁-Adrenergic Receptor Blockade Attenuates Angiotensin II–Mediated Catecholamine Release Into the Cardiac Interstitium in Mitral Regurgitation

José Tallaj, MD; Chih-Chang Wei, PhD; Gerald H. Hankes, DVM, PhD; Merrilee Holland, DVM; Patricia Rynders, DVM; A. Ray Dillon, DVM; Jeffrey L. Ardell, PhD; J. Andrew Armour, MD, PhD; Pamela A. Lucchesi, PhD; Louis J. Dell’Italia, MD

From the Department of Medicine (J.T., C.-C.W., P.A.L., L.J.D.), Division of Cardiovascular Disease, Department of Veterans Affairs (L.J.D.), University of Alabama at Birmingham; College of Veterinary Medicine (G.H.H., M.H., P.R., A.R.D.), Auburn University, Auburn, Ala; the Department of Pharmacology (J.L.A.), East Tennessee State University, Johnson City, Tenn; and the Department of Pharmacology (J.A.A.), University of Montreal, Montreal, Quebec, Canada.

Reprint requests to Louis J. Dell’Italia, MD, Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, 834 MCLM, 1530 3rd Ave S, 1918 University Blvd, Birmingham, AL. E-mail dell'italia{at}physiology.uab.edu

Background— This study tested the hypothesis that ß₁-adrenoreceptor blockade modulates the angiotensin II (Ang II)–evoked neural release of norepinephrine (NE) and epinephrine (Epi) into the cardiac interstitial fluid (ISF) space in experimentally induced mitral regurgitation (MR) in the dog.

Methods and Results— Normal dogs (n=8) were compared with dogs with MR of 2 (n=8) and 4 (n=6) weeks’ duration and with dogs with MR treated with ß₁-receptor blockade (RB; extended-release metoprolol succinate, 100 mg QD; MR+ß₁-RB) that was started 24 hours after MR induction for 2 (n=6) and 4 weeks (n=8). Left ventricular end-diastolic dimension increased 20% as plasma Ang II levels increased >5-fold in both MR and MR+ß₁-RB dogs at 2 and 4 weeks. Ang II infusion into the left atrium produced increases in ISF NE and Epi in normal dogs, which were further increased in 2- and 4-week MR dogs but were restored to normal in 4-week MR+ß₁-RB dogs. Ang II infusion produced 4-fold increases in circulating NE and Epi in 2- and 4-week MR dogs that returned to normal in 4-week+ß₁-RB dogs. Left ventricular angiotensin-converting enzyme activity and ISF Ang II were increased in 4-week MR dogs but were decreased in 4-week MR+ß₁-RB dogs.

Conclusions— ß₁-RB decreases renin-angiotensin system sympathostimulation and activation by attenuating the Ang II–mediated NE and Epi release into the cardiac ISF and circulation and by decreasing left ventricular angiotensin-converting enzyme expression in the early phases of volume overload.

Key Words: angiotensin • nervous system, autonomic • receptors, adrenergic, beta • heart failure • renin

This article has been cited by other articles:

				J. L. Ardell, R. Cardinal, M. Vermeulen, and J. A. Armour Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R470 - R477. [Abstract] [Full Text] [PDF]

				J. A. Dixon and F. G. Spinale Large Animal Models of Heart Failure: A Critical Link in the Translation of Basic Science to Clinical Practice Circ Heart Fail, May 1, 2009; 2(3): 262 - 271. [Abstract] [Full Text] [PDF]

				J. Zheng, Y. Chen, B. Pat, L. A. Dell'Italia, M. Tillson, A. R. Dillon, P. C. Powell, K. Shi, N. Shah, T. Denney, et al. Microarray Identifies Extensive Downregulation of Noncollagen Extracellular Matrix and Profibrotic Growth Factor Genes in Chronic Isolated Mitral Regurgitation in the Dog Circulation, April 21, 2009; 119(15): 2086 - 2095. [Abstract] [Full Text] [PDF]

				B. Pat, C. Killingsworth, T. Denney, J. Zheng, P. Powell, M. Tillson, A. R. Dillon, and L. J. Dell'Italia Dissociation between cardiomyocyte function and remodeling with {beta}-adrenergic receptor blockade in isolated canine mitral regurgitation Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2321 - H2327. [Abstract] [Full Text] [PDF]

				A. Sabri, K. Rafiq, R. Seqqat, M. A. Kolpakov, R. Dillon, and L. J. Dell'italia Sympathetic Activation Causes Focal Adhesion Signaling Alteration in Early Compensated Volume Overload Attributable to Isolated Mitral Regurgitation in the Dog Circ. Res., May 9, 2008; 102(9): 1127 - 1136. [Abstract] [Full Text] [PDF]

				G. H. Hankes, J. L. Ardell, J. Tallaj, C.-C. Wei, I. Aban, M. Holland, P. Rynders, R. Dillon, R. Cardinal, D. B. Hoover, et al. beta1-Adrenoceptor blockade mitigates excessive norepinephrine release into cardiac interstitium in mitral regurgitation in dog Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H147 - H151. [Abstract] [Full Text] [PDF]

				J. A. Armour Cardiac neuronal hierarchy in health and disease Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R262 - R271. [Abstract] [Full Text] [PDF]

				R. C. Arora, R. Cardinal, F. M. Smith, J. L. Ardell, L. J. Dell'Italia, and J. A. Armour Intrinsic cardiac nervous system in tachycardia induced heart failure Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1212 - R1223. [Abstract] [Full Text] [PDF]