Published Online
on July 11, 2005

A more recent version of this article appeared on August 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/2/333    most recent 01.HYP.0000178157.70142.33v1 Alert me when this article is cited Alert me if a correction is posted 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 Sakima, A. Articles by Diz, D. I. Search for Related Content PubMed PubMed Citation Articles by Sakima, A. Articles by Diz, D. I. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Seniors' Health Related Collections ACE/Angiotension receptors Other hypertension Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation

Submitted on February 21, 2005
Revised on March 17, 2005

Impaired Heart Rate Baroreflex in Older Rats. Role of Endogenous Angiotensin-(1-7) at the Nucleus Tractus Solitarii

Atsushi Sakima; David B. Averill; Patricia E. Gallagher; Sherry O. Kasper; Ellen N. Tommasi; Carlos M. Ferrario; and Debra I. Diz^*

The Hypertension and Vascular Disease Center, Department of General Surgery and Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC.

^* To whom correspondence should be addressed. E-mail: ddiz{at}wfubmc.edu.

Abstract--Age-related baroreflex reductions in function may originate from central neural dysregulation as well as vascular structural/functional changes. We determined the role of 2 angiotensin (Ang) peptides at the nucleus tractus solitarii in age-related baroreflex impairment. Baroreflex sensitivity control of heart rate in response to increases in blood pressure was tested in younger (3 to 5 months) and older (16 to 20 months) anesthetized male Sprague-Dawley rats before and after bilateral solitary tract injections of the Ang II type 1 (AT₁) receptor antagonist candesartan (24 pmol) or the Ang-(1-7) antagonist (D-Ala⁷)-Ang-(1-7) (144 fmol or 24 pmol). Basal reflex sensitivity of older rats was significantly lower than younger rats. In younger rats, the reflex was facilitated by bilateral candesartan injections and attenuated by bilateral (D-Ala⁷)-Ang-(1-7) injections. In older rats, the reflex was facilitated by AT₁ blockade; however, (D-Ala⁷)-Ang-(1-7) injected into the solitary tract nucleus had no effect. Neprilysin mRNA in the medulla was lower in older rats compared with younger rats, whereas angiotensin-converting enzyme (ACE), ACE2, and mas receptor mRNA levels of older rats did not differ from values of younger rats. Thus, opposing actions of endogenous Ang II and Ang-(1-7) in the solitary tract nucleus contribute to baroreflex function in response to increases in mean arterial pressure of younger rats. The attenuated counterbalancing effect of Ang-(1-7) on baroreflex function is lost in older rats, which may be attributable to diminished production of the peptide from neprilysin.

Key words: baroreceptors • angiotensin • aging

This article has been cited by other articles:

				V. M. Pulgar, J. K.-s. Hong, J. A. Jessup, A. G. Massmann, D. I. Diz, and J. P. Figueroa Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R446 - R452. [Abstract] [Full Text] [PDF]

				H. Xia, Y. Feng, T. D. Obr, P. J. Hickman, and E. Lazartigues Angiotensin II Type 1 Receptor-Mediated Reduction of Angiotensin-Converting Enzyme 2 Activity in the Brain Impairs Baroreflex Function in Hypertensive Mice Hypertension, February 1, 2009; 53(2): 210 - 216. [Abstract] [Full Text] [PDF]

				D. I. Diz Future Directions in Cardiovascular Pharmacology: Examples from the Renin-Angiotensin System Mol. Interv., October 1, 2008; 8(5): 222 - 225. [Abstract] [Full Text] [PDF]

				C. J. Thomas, R. M. McAllen, L. M. Salo, and R. L. Woods Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats Hypertension, October 1, 2008; 52(4): 696 - 701. [Abstract] [Full Text] [PDF]

				D. I. Diz Lewis K. Dahl Memorial Lecture: The Renin-Angiotensin System and Aging Hypertension, July 1, 2008; 52(1): 37 - 43. [Full Text] [PDF]

				K. M. Elased, T. S. Cunha, F. K. Marcondes, and M. Morris Brain angiotensin-converting enzymes: role of angiotensin-converting enzyme 2 in processing angiotensin II in mice Exp Physiol, May 1, 2008; 93(5): 665 - 675. [Abstract] [Full Text] [PDF]

				Z. Lin, Y. Chen, W. Zhang, A. F. Chen, S. Lin, and M. Morris RNA interference shows interactions between mouse brainstem angiotensin AT1 receptors and angiotensin-converting enzyme 2 Exp Physiol, May 1, 2008; 93(5): 676 - 684. [Abstract] [Full Text] [PDF]

				D. I. Diz, M. A. Garcia-Espinosa, S. Gegick, E. N. Tommasi, C. M. Ferrario, E. Ann Tallant, M. C. Chappell, and P. E. Gallagher Injections of angiotensin-converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats Exp Physiol, May 1, 2008; 93(5): 694 - 700. [Abstract] [Full Text] [PDF]

				A. C. Arnold, A. Sakima, D. Ganten, C. M. Ferrario, and D. I. Diz Modulation of Reflex Function by Endogenous Angiotensins in Older Transgenic Rats With Low Glial Angiotensinogen Hypertension, May 1, 2008; 51(5): 1326 - 1331. [Abstract] [Full Text] [PDF]

				Y. Feng, X. Yue, H. Xia, S. M. Bindom, P. J. Hickman, C. M. Filipeanu, G. Wu, and E. Lazartigues Angiotensin-Converting Enzyme 2 Overexpression in the Subfornical Organ Prevents the Angiotensin II-Mediated Pressor and Drinking Responses and Is Associated With Angiotensin II Type 1 Receptor Downregulation Circ. Res., March 28, 2008; 102(6): 729 - 736. [Abstract] [Full Text] [PDF]

				M. C. Chappell Emerging Evidence for a Functional Angiotensin-Converting Enzyme 2-Angiotensin-(1-7)-Mas Receptor Axis: More Than Regulation of Blood Pressure? Hypertension, October 1, 2007; 50(4): 596 - 599. [Full Text] [PDF]

				K. D. Monahan Effect of aging on baroreflex function in humans Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R3 - R12. [Abstract] [Full Text] [PDF]

				M. Yamazato, Y. Yamazato, C. Sun, C. Diez-Freire, and M. K. Raizada Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Causes Long-Term Decrease in Blood Pressure in the Spontaneously Hypertensive Rats Hypertension, April 1, 2007; 49(4): 926 - 931. [Abstract] [Full Text] [PDF]

				A. Sakima, D. B. Averill, S. O. Kasper, L. Jackson, D. Ganten, C. M. Ferrario, P. E. Gallagher, and D. I. Diz Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1412 - H1419. [Abstract] [Full Text] [PDF]

				M. F. Doobay, L. S. Talman, T. D. Obr, X. Tian, R. L. Davisson, and E. Lazartigues Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R373 - R381. [Abstract] [Full Text] [PDF]