The spontaneously hypertensive rat (SHR) is the most widely studied animal model of high blood pressure. This strain, like many humans with essential hypertension, exhibits insulin resistance and dyslipidemia as well as increased blood pressure. However, the primary mechanisms We found that transferring a piece of chromosome 4 form the normotensive Brown Norway (BN) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) in the SHR-chr 4 congenic strain. A deletion in the Cd36 gene that encodes a fatty acid transporter has been found to be responsible for the SHR defects in fatty acid/lipid metabolism associated with this region of chromosome 4. However, molecular and physiologic studies indicate that the mutant form of Cd36 is not likely to be responsible for the effect of this chromosome region on BP and insulin resistance. In the current studies, we propose to derived and phenotype multiple recombinant congenic sublines to genetically dissect the association of insulin resistance and hypertension and further investigate the clustering of multiple cardiovascular in this model.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
1R03TW001236-01A1
Application #
6288380
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Primack, Aron
Project Start
2001-02-09
Project End
2004-01-31
Budget Start
2001-02-09
Budget End
2002-01-31
Support Year
1
Fiscal Year
2001
Total Cost
$36,420
Indirect Cost
Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Pravenec, Michal; Kazdova, Ludmila; Landa, Vladimir et al. (2008) Identification of mutated Srebf1 as a QTL influencing risk for hepatic steatosis in the spontaneously hypertensive rat. Hypertension 51:148-53
Pravenec, M; Kazdova, L; Cahova, M et al. (2006) Fat-specific transgenic expression of resistin in the spontaneously hypertensive rat impairs fatty acid re-esterification. Int J Obes (Lond) 30:1157-9
Pravenec, M; Landa, V; Zidek, V et al. (2003) Transgenic expression of CD36 in the spontaneously hypertensive rat is associated with amelioration of metabolic disturbances but has no effect on hypertension. Physiol Res 52:681-8
Pravenec, Michal; Wallace, Caroline; Aitman, Timothy J et al. (2003) Gene expression profiling in hypertension research: a critical perspective. Hypertension 41:3-8
Pravenec, Michal; Kazdova, Ludmila; Landa, Vladimir et al. (2003) Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat. J Biol Chem 278:45209-15
Qi, Nianning; Kazdova, Ludmila; Zidek, Vaclav et al. (2002) Pharmacogenetic evidence that cd36 is a key determinant of the metabolic effects of pioglitazone. J Biol Chem 277:48501-7
Pravenec, Michal; Kurtz, Theodore W (2002) Genetics of Cd36 and the hypertension metabolic syndrome. Semin Nephrol 22:148-53