Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression in hypertensive rats
Reja, V., Goodchild, A.K., Phillips, J.K. and Pilowsky, P.M. (2006) Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression in hypertensive rats. Clinical and Experimental Pharmacology and Physiology, 33 (8). pp. 690-695.
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1. Activation of angiotensin II AT1 receptors (AT1R) stimulates catecholamine systems within both central and peripheral tissues that are associated with blood pressure control. In the present study, we sought to determine whether the hypertensive phenotype of the spontaneously hypertensive rat (SHR) is associated with changes in AT1R gene expression and whether gene expression of downstream signalling molecules was coupled to catecholamine gene expression, both in key brainstem nuclei and in peripheral sites implicated in cardiovascular control.
2. Gene expression levels of AT1R, extracellular signal-regulated kinase (ERK) 1 and 2 and phosphatidylinositol 3-kinase (PI3-K) were quantified in Wistar-Kyoto (WKY) rats and SHR. Messenger RNA expression levels were quantified using real time reverse transcription–polymerase chain reaction. In addition, we investigated whether there was a relationship between gene expression and systolic blood pressure.
3. The gene expression levels of AT1R, ERK2 and PI3-K were significantly higher in the paraventricular nucleus of the hypothalamus (4.12-, 1.40- and 1.38-fold, respectively), rostral ventrolateral medulla (2.71-, 1.33- and 2.73-fold, respectively), spinal cord (30.5-, 2.72- and 1.53-fold, respectively), adrenal medulla (1.68-, 1.55- and 1.76-fold, respectively) and coeliac ganglion (1.39-, 1.35- and 1.12-fold, respectively) in SHR compared with WKY rats. There was no significant difference in the level of ERK1 gene expression between the two strains. The gene expression levels of AT1R and ERK2 were positively correlated with blood pressure in all central nervous tissues investigated in the SHR, but not in WKY rats. Gene expression levels of the AT1R in the coeliac ganglion and adrenal medulla were also positively correlated with increased systolic blood pressure.
4. The present data suggest that a defect in AT1R expression (that may further alter downstream signalling pathways) in the SHR may be responsible, at least in part, for the hypertensive phenotype.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Biomedical Sciences|
|Copyright:||2006 Blackwell Publishing Asia Pty Ltd|
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