This Article Full Text Full Text (PDF) 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 Chan, J. Y.H. Articles by Chan, S. H.H. Search for Related Content PubMed PubMed Citation Articles by Chan, J. Y.H. Articles by Chan, S. H.H. Related Collections Autonomic, reflex, and neurohumoral control of circulation

(Circulation. 2001;104:1676.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Reduced Functional Expression and Molecular Synthesis of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

Julie Y.H. Chan, PhD; Ling-Lin Wang, MS; Kay L.H. Wu, MS; Samuel H.H. Chan, PhD

From the Department of Medical Education and Research, Kaohsiung Veterans General Hospital (J.Y.H.C, L.L.W., K.L.H.W.), and Center for Neuroscience, National Sun Yat-sen University (S.H.H.C.), Kaohsiung, Taiwan, Republic of China.

Correspondence to Julie Y.H. Chan, PhD, Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81346, Taiwan, Republic of China. E-mail yhwa{at}isca.vghks.gov.tw

Background— We demonstrated recently that the prevalence of neuronal (nNOS) over inducible (iNOS) nitric oxide synthase activity at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone, and the associated dominance of sympathoexcitation over sympathoinhibition underlie the maintenance of sympathetic vasomotor outflow by the endogenous NO. Here, we evaluated the hypothesis that a significant downregulation of iNOS at the RVLM may play a crucial role in the genesis of augmented sympathetic vasomotor tone during hypertension.

Methods and Results— Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized with propofol were used. Compared with SHR, the hypotension, bradycardia, or depression in sympathetic vasomotor tone induced by bilateral microinjection of lipopolysaccharide (5 or 10 ng) into the RVLM of WKY rats exhibited significantly shorter-onset latency, appreciably steeper slope, and a greater incidence of mortality. All these effects of lipopolysaccharide (10 ng) were significantly blunted by coadministration of the selective iNOS inhibitor S-methylisothiourea (250 pmol). Reverse transcription-polymerase chain reaction and Western blot analyses further revealed significantly lower iNOS mRNA and protein levels at the ventrolateral medulla in SHR under basal conditions or on activation by lipopolysaccharide (10 ng). Conversely, nNOS mRNA and protein levels remained constant in the RVLM and were comparable in both strains of rats.

Conclusions— We conclude that a significant downregulation in both functional expression and molecular synthesis of iNOS at the RVLM may underlie the augmented sympathetic vasomotor tone during hypertension.

Key Words: blood pressure • heart rate • hypertension • nervous system, sympathetic • nitric oxide synthase

This article has been cited by other articles:

				J. Peng, Y.-K. Wang, L.-G. Wang, W.-J. Yuan, D.-F. Su, X. Ni, X.-M. Deng, and W.-Z. Wang Sympathoinhibitory mechanism of moxonidine: role of the inducible nitric oxide synthase in the rostral ventrolateral medulla Cardiovasc Res, November 1, 2009; 84(2): 283 - 291. [Abstract] [Full Text] [PDF]

				Z.-L. Guo, S. C. Tjen-A-Looi, L.-W. Fu, and J. C. Longhurst Nitric oxide in rostral ventrolateral medulla regulates cardiac-sympathetic reflexes: role of synthase isoforms Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1478 - H1486. [Abstract] [Full Text] [PDF]

				L. Gao, W. Wang, and I. H. Zucker Simvastatin Inhibits Central Sympathetic Outflow in Heart Failure by a Nitric-Oxide Synthase Mechanism J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 278 - 285. [Abstract] [Full Text] [PDF]

				M.-H. Tai, W.-T. Weng, W.-C. Lo, J. Y. H. Chan, C.-J. Lin, H.-C. Lam, and C.-J. Tseng Role of Nitric Oxide in {alpha}-Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 455 - 461. [Abstract] [Full Text] [PDF]

				C. E. Wood and D. Giroux Expression of Nitric Oxide Synthase Isoforms in the Ovine Fetal Brain: Alteration by Hormonal and Hemodynamic Stimuli Reproductive Sciences, July 1, 2006; 13(5): 329 - 337. [Abstract] [PDF]

				S. Racasan, B. Braam, H. A. Koomans, and J. A. Joles Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon Am J Physiol Renal Physiol, April 1, 2005; 288(4): F626 - F636. [Abstract] [Full Text] [PDF]

				L.-L. Wang, C.-C. Ou, and J. Y.H. Chan Receptor-Independent Activation of GABAergic Neurotransmission and Receptor-Dependent Nontranscriptional Activation of Phosphatidylinositol 3-kinase/Protein Kinase Akt Pathway in Short-Term Cardiovascular Actions of Dexamethasone at the Nucleus Tractus Solitarii of the Rat Mol. Pharmacol., February 1, 2005; 67(2): 489 - 498. [Abstract] [Full Text] [PDF]

				J. Y.H. Chan, L.-L. Wang, C.-C. Ou, and S. H.H. Chan Downregulation of Angiotensin Subtype 1 Receptor in Rostral Ventrolateral Medulla During Endotoxemia Hypertension, July 1, 2003; 42(1): 103 - 109. [Abstract] [Full Text] [PDF]

				J. Y.H. Chan, L.-L. Wang, Y.-M. Chao, and S. H.H. Chan Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR Hypertension, March 1, 2003; 41(3): 563 - 570. [Abstract] [Full Text] [PDF]