This Article Full Text 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 Huang, B. S. Articles by Leenen, F. H. H. Search for Related Content PubMed PubMed Citation Articles by Huang, B. S. Articles by Leenen, F. H. H.

(Circulation. 1997;96:1654-1659.)
© 1997 American Heart Association, Inc.

Articles

Blockade of Brain `Ouabain' Prevents the Impairment of Baroreflexes in Rats After Myocardial Infarction

Bing S. Huang, MD, PhD; Baoxue Yuan, MD; ; Frans H. H. Leenen, MD, PhD, FRCPC

From the University of Ottawa (Ontario) Heart Institute, Canada.

Correspondence to Frans H.H. Leenen, MD, PhD, FRCPC, Hypertension Unit, H360, Division of Cardiology, University of Ottawa Heart Institute, 1053 Carling Ave, Ottawa, Ontario, Canada, K1Y 4E9. E-mail fleenen{at}ohi-net.heartinst.on.ca

Background The purpose of this study was to test whether increased brain "ouabain" contributes to impairment of both arterial and cardiopulmonary baroreceptor reflexes in congestive heart failure (CHF).

Methods and Results Two to 5 days after coronary artery ligation (MI) or sham surgery in male Wistar rats, chronic intracerebroventricular (ICV) infusion was started with either antibody Fab fragments, which bind ouabain and related steroids with high affinity, or -globulins as control (200 µg · 12 µL^-1 · d^-1 for both) with osmotic minipumps implanted subcutaneously. After 8 weeks of infusion, in conscious rats, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and renal sympathetic nerve activity (RSNA) were recorded at rest and in response to ramp changes in blood pressure (BP) induced by intravenous phenylephrine and nitroprusside and to changes in CVP elicited by acute volume expansion with 5% dextrose. Compared with sham rats, in MI rats with ICV -globulins, resting MAP was significantly lower and CVP increased, and both arterial and cardiopulmonary baroreflex control of RSNA and HR were attenuated. ICV Fab fragments prevented the decrease in resting BP and largely prevented impairment of arterial and cardiopulmonary baroreflex control of both RSNA and HR.

Conclusions These data indicate that increased brain ouabain plays a major role in the impairment of baroreflexes in rats with CHF after myocardial infarction.

Key Words: heart failure • nervous system, autonomic • ouabain, brain • baroreceptors

This article has been cited by other articles:

				H. Wang, B. S. Huang, D. Ganten, and F. H.H. Leenen Prevention of Sympathetic and Cardiac Dysfunction After Myocardial Infarction in Transgenic Rats Deficient in Brain Angiotensinogen Circ. Res., April 2, 2004; 94(6): 843 - 849. [Abstract] [Full Text] [PDF]

				T. Sato, T. Kawada, M. Inagaki, T. Shishido, M. Sugimachi, and K. Sunagawa Dynamics of sympathetic baroreflex control of arterial pressure in rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R262 - R270. [Abstract] [Full Text] [PDF]

				R. B. Felder, J. Francis, Z.-H. Zhang, S.-G. Wei, R. M. Weiss, and A. K. Johnson Heart failure and the brain: new perspectives Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R259 - R276. [Abstract] [Full Text] [PDF]

				D. L. Jardine, C. J. Charles, I. C. Melton, C. N. May, M. D. Forrester, C. M. Frampton, S. I. Bennett, and H. Ikram Continual recordings of cardiac sympathetic nerve activity in conscious sheep Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H93 - H99. [Abstract] [Full Text] [PDF]

				F. H. H. Leenen, B. Yuan, and B. S. Huang Brain "ouabain" and angiotensin II contribute to cardiac dysfunction after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1786 - H1792. [Abstract] [Full Text] [PDF]

				Y. Murasato, Y. Harada, M. Ikeda, Y. Nakashima, and Y. Hayashida Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats Hypertension, August 1, 1999; 34(2): 247 - 252. [Abstract] [Full Text] [PDF]

				T. Sato, T. Kawada, M. Inagaki, T. Shishido, H. Takaki, M. Sugimachi, and K. Sunagawa New analytic framework for understanding sympathetic baroreflex control of arterial pressure Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2251 - H2261. [Abstract] [Full Text] [PDF]

				W. Zhang, B. S. Huang, and F. H. H. Leenen Brain renin-angiotensin system and sympathetic hyperactivity in rats after myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1608 - H1615. [Abstract] [Full Text] [PDF]

				F. Vahid-Ansari and F. H. H. Leenen Pattern of neuronal activation in rats with CHF after myocardial infarction Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2140 - H2146. [Abstract] [Full Text] [PDF]