This Article Full Text Full Text (PDF) All Versions of this Article: 42/5/1026    most recent 01.HYP.0000097603.55404.35v1 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 Zhao, C. Articles by Zeldin, D. C. Search for Related Content PubMed PubMed Citation Articles by Zhao, C. Articles by Zeldin, D. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB FRUCTOSE Medline Plus Health Information Genes and Gene Therapy High Blood Pressure Related Collections Other hypertension Gene therapy ACE/Angiotension receptors Animal models of human disease Hypertension - basic studies

(Hypertension. 2003;42:1026.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Gene Therapy With Human Tissue Kallikrein Reduces Hypertension and Hyperinsulinemia in Fructose-Induced Hypertensive Rats

Chunxia Zhao; Peihua Wang; Xiao Xiao; Julie Chao; Lee Chao; Dao Wen Wang; Darryl C. Zeldin

From the Cardiovascular Division of Internal Medicine, Department and Gene Therapy Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (C.Z., P.W., X.X., D.W.W.), Wuhan, Peoples Republic of China; the Department of Biochemistry, Medical University of South Carolina (J.C., L.C.), Charleston; and the Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health (D.C.Z.), Research Triangle Park, NC.

Correspondence to Dao Wen Wang, MD, PhD, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PRC. E-mail dwwang{at}tjh.tjmu.edu.cn

This study investigates gene therapy with human tissue kallikrein as a treatment for fructose-induced hypertension in rats. Hypertension was induced by addition of 10% fructose to drinking water. Fructose-fed rats also had increased serum insulin and triglycerides, decreased urine osmolarity, increased urine volume and endothelin-1, and increased aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels. Fructose-induced hypertensive and control rats were injected intravenously with a construct containing the human tissue kallikrein cDNA. Two weeks after injection of hypertensive rats, systolic blood pressure and serum insulin levels normalized, urine osmolarity increased, urine endothelin-1 levels decreased, and aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels decreased. In contrast, injection of the human tissue kallikrein cDNA had minimal effect on blood pressure or insulin levels in control rats. These results suggest that gene therapy with human tissue kallikrein may have potential as a treatment for hypertension and associated insulin resistance. Moreover, our data suggest that the beneficial effects of human tissue kallikrein on these parameters are associated with changes in endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 expression.

Key Words: kinins • diabetes mellitus • hypertension, renal • endothelin • receptors, endothelin • angiotensin II

This article has been cited by other articles:

				G. Yuan, J. Deng, T. Wang, C. Zhao, X. Xu, P. Wang, J. W. Voltz, M. L. Edin, X. Xiao, L. Chao, et al. Tissue Kallikrein Reverses Insulin Resistance and Attenuates Nephropathy in Diabetic Rats by Activation of Phosphatidylinositol 3-Kinase/Protein Kinase B and Adenosine 5'-Monophosphate-Activated Protein Kinase Signaling Pathways Endocrinology, May 1, 2007; 148(5): 2016 - 2026. [Abstract] [Full Text] [PDF]

				P. M. Abadir, A. Periasamy, R. M. Carey, and H. M. Siragy Angiotensin II Type 2 Receptor-Bradykinin B2 Receptor Functional Heterodimerization Hypertension, August 1, 2006; 48(2): 316 - 322. [Abstract] [Full Text] [PDF]

				L. J. Mullins, M. A. Bailey, and J. J. Mullins Hypertension, Kidney, and Transgenics: A Fresh Perspective Physiol Rev, April 1, 2006; 86(2): 709 - 746. [Abstract] [Full Text] [PDF]

				D. Y. Huang, K. M. Boini, B. Friedrich, M. Metzger, L. Just, H. Osswald, P. Wulff, D. Kuhl, V. Vallon, and F. Lang Blunted hypertensive effect of combined fructose and high-salt diet in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1 Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R935 - R944. [Abstract] [Full Text] [PDF]

				M. K. Raizada and S. D. Sarkissian Potential of Gene Therapy Strategy for the Treatment of Hypertension Hypertension, January 1, 2006; 47(1): 6 - 9. [Full Text] [PDF]

				J. Chao and L. Chao Kallikrein-kinin in stroke, cardiovascular and renal disease Exp Physiol, May 1, 2005; 90(3): 291 - 298. [Abstract] [Full Text] [PDF]