This Article Full Text Full Text (PDF) All Versions of this Article: 45/4/786    most recent 01.HYP.0000154879.49245.39v1 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 McBride, M. W. Articles by Dominiczak, A. F. Search for Related Content PubMed PubMed Citation Articles by McBride, M. W. Articles by Dominiczak, A. F. Related Collections Animal models of human disease Other hypertension Functional genomics Gene expression Gene regulation Endothelium/vascular type/nitric oxide

(Hypertension. 2005;45:786.)
© 2005 American Heart Association, Inc.

Original Articles

Reduction of Gstm1 Expression in the Stroke-Prone Spontaneously Hypertension Rat Contributes to Increased Oxidative Stress

Martin W. McBride; M. Julia Brosnan; Joanne Mathers; Lesley I. McLellan; William H. Miller; Delyth Graham; Neil Hanlon; Carlene A. Hamilton; James M. Polke; Wai K. Lee; Anna F. Dominiczak

From the BHF Glasgow Cardiovascular Research Centre (M.W.M., M.J.B., W.H.M., D.G., N.H., C.A.H., J.M.P., W.K.L., A.F.D.), Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom; and Biomedical Research Centre (J.M., L.I.M.), University of Dundee, Ninewells Hospital and Medical School, United Kingdom.

Correspondence to Professor Anna F. Dominiczak, BHF Glasgow Cardiovascular Research Centre, University of Glasgow G11 6NT. E-mail ad7e{at}clinmed.gla.ac.uk

Human essential hypertension is a classic example of a complex, multifactorial, polygenic disease with a substantial genetic influence in which the underlying genetic components remain unknown. The stroke-prone spontaneously hypertension rat (SHRSP) is a well-characterized experimental model for essential hypertension and endothelial dysfunction. Previous work, identified glutathione S-transferase µ type 1, a protein involved in detoxification of reactive oxygen species, as a positional and functional candidate gene. Quantitative real-time polymerase chain reaction showed a highly significant, 4-fold reduction of glutathione S-transferase µ type 1 mRNA expression in 5- and 16-week-old SHRSP compared with the congenic and normotensive Wistar Kyoto rats. This suggests that differential expression is not attributable to long-term changes in blood pressure. DNA sequencing identified one coding single nucleotide polymorphism (R202H) and multiple single nucleotide polymorphisms in the promoter region. mRNA expression changes were reflected at the protein level, with significant reductions in the SHRSP glutathione S-transferase µ type 1. Protein was colocalized with aquaporin 2 to the principle cells of the renal collecting ducts. Coupled to significant increases in nitrotyrosine levels in the kidney, this suggests a pathophysiological role of this protein in hypertension and oxidative stress. Similar processes may underlie oxidative stress in the vasculature.

Key Words: rats, stroke-prone SHR • hypertension, genetic • gene expression • oxidative stress

This article has been cited by other articles:

				D. Graham, N. N. Huynh, C. A. Hamilton, E. Beattie, R. A.J. Smith, H. M. Cocheme, M. P. Murphy, and A. F. Dominiczak Mitochondria-Targeted Antioxidant MitoQ10 Improves Endothelial Function and Attenuates Cardiac Hypertrophy Hypertension, August 1, 2009; 54(2): 322 - 328. [Abstract] [Full Text] [PDF]

				W. J. Welch Angiotensin II-Dependent Superoxide: Effects on Hypertension and Vascular Dysfunction Hypertension, July 1, 2008; 52(1): 51 - 56. [Full Text] [PDF]

				N. H. Lee, B. J. Haas, N. E. Letwin, B. C. Frank, T. V. Luu, Q. Sun, C. D. House, S. Yerga-Woolwine, P. Farms, E. Manickavasagam, et al. Cross-Talk of Expression Quantitative Trait Loci Within 2 Interacting Blood Pressure Quantitative Trait Loci Hypertension, December 1, 2007; 50(6): 1126 - 1133. [Abstract] [Full Text] [PDF]

				D. Graham, M. W. McBride, M. Gaasenbeek, K. Gilday, E. Beattie, W. H. Miller, J. D. McClure, J. M. Polke, A. Montezano, R. M. Touyz, et al. Candidate Genes That Determine Response to Salt in the Stroke-Prone Spontaneously Hypertensive Rat: Congenic Analysis Hypertension, December 1, 2007; 50(6): 1134 - 1141. [Abstract] [Full Text] [PDF]

				M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]

				B. Joe, N. E. Letwin, M. R. Garrett, S. Dhindaw, B. Frank, R. Sultana, K. Verratti, J. P. Rapp, and N. H. Lee Transcriptional profiling with a blood pressure QTL interval-specific oligonucleotide array Physiol Genomics, November 17, 2005; 23(3): 318 - 326. [Abstract] [Full Text] [PDF]

				T. H. Westhoff, S. Scheid, M. Tolle, B. Kaynak, S. Schmidt, W. Zidek, S. Sperling, and M. van der Giet A physiogenomic approach to study the regulation of blood pressure Physiol Genomics, September 21, 2005; 23(1): 46 - 53. [Abstract] [Full Text] [PDF]