title: Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets.
abstract: BACKGROUND
  Hypertension is a complex disease with many contributory genetic and environmental factors. We aimed to identify common targets for therapy by gene expression profiling of a resistance artery taken from animals representing two different models of hypertension. We studied gene expression and morphology of a saphenous artery branch in normotensive WKY rats, spontaneously hypertensive rats (SHR) and adrenocorticotropic hormone (ACTH)-induced hypertensive rats.
  
  
  RESULTS
  Differential remodeling of arteries occurred in SHR and ACTH-treated rats, involving changes in both smooth muscle and endothelium. Increased expression of smooth muscle cell growth promoters and decreased expression of growth suppressors confirmed smooth muscle cell proliferation in SHR but not in ACTH. Differential gene expression between arteries from the two hypertensive models extended to the renin-angiotensin system, MAP kinase pathways, mitochondrial activity, lipid metabolism, extracellular matrix and calcium handling. In contrast, arteries from both hypertensive models exhibited significant increases in caveolin-1 expression and decreases in the regulators of G-protein signalling, Rgs2 and Rgs5. Increased protein expression of caveolin-1 and increased incidence of caveolae was found in both smooth muscle and endothelial cells of arteries from both hypertensive models.
  
  
  CONCLUSIONS
  We conclude that the majority of differences in gene expression found in the saphenous artery taken from rats with two different forms of hypertension reflect distinctive morphological and physiological alterations. However, changes in common to caveolin-1 expression and G protein signalling, through attenuation of Rgs2 and Rgs5, may contribute to hypertension through augmentation of vasoconstrictor pathways and provide potential targets for common drug development.
authors.affiliation: Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia. hilton.grayson@anu.edu.au
authors.forename: T Hilton
authors.initials: TH
authors.lastname: Grayson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ohms
authors.forename: Therese D
authors.initials: TD
authors.lastname: Brackenbury
authors.forename: Kate R
authors.initials: KR
authors.lastname: Meaney
authors.forename: Kaiman
authors.initials: K
authors.lastname: Peng
authors.forename: Yvonne E
authors.initials: YE
authors.lastname: Pittelkow
authors.forename: Susan R
authors.initials: SR
authors.lastname: Wilson
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: Caryl E
authors.initials: CE
authors.lastname: Hill
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics*; D020869:Gene Expression Profiling; D006973:Hypertension / Q000235:genetics*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020710:RGS Proteins / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
chemical_list: D051242:Caveolin 1; D020710:RGS Proteins; C514563:RGS2 protein, rat; C491348:Rgs5 protein, rat