Vascular thrombin receptor regulation in hypertensive rats

Circulation Research
Q CapersW R Taylor

Abstract

Thrombin has been implicated as an important mediator of vascular lesion formation in atherosclerosis and restenosis. To investigate a potential role for thrombin signaling in the vascular response to hypertension, we have studied thrombin receptor (TR) expression and regulation in hypertensive rats. Aortic TR mRNA was upregulated by angiotensin II (Ang II)-induced hypertension (10.7 +/- 2.5 times control, P < .02), which correlated with a 4-fold increase in thrombin-induced constriction in isolated endothelium-denuded aortic rings. The AT1 receptor antagonist losartan normalized blood pressure and TR mRNA. Conversely, lowering blood pressure to the same degree with hydralazine did not abolish the upregulation of TR mRNA expression. When low-renin low-Ang II hypertension was induced in Dahl salt-sensitive rats, there was no detectable increase in the expression of aortic thrombin receptor mRNA. Finally, treatment with a chimeric heparin-binding form of the recombinant human Cu/Zn superoxide dismutase caused complete inhibition of TR mRNA upregulation, suggesting that an increased rate of superoxide anion production is an important signaling mechanism. Thus, increased TR expression via a redox-sensitive mechanism in the aortic s...Continue Reading

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Citations

Sep 12, 2000·Current Hypertension Reports·H M Siragy, M Bedigian
Sep 12, 2000·Current Hypertension Reports·W R Taylor
Jan 1, 1995·Cellular Signalling·S F LawT Reisine
Sep 1, 2000·Regulatory Peptides·K K Griendling, M Ushio-Fukai
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Sep 14, 2011·Hypertension·Elena Y SenchenkovaD Neil Granger
Dec 30, 2011·PloS One·Lun Yang, Pankaj Agarwal
Dec 29, 2005·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Takanori Karasawa, Masao Sugawara
Jun 14, 2014·Vascular Pharmacology·Maria Adele Alberelli, Erica De Candia
Feb 14, 2012·Pharmacology & Therapeutics·Hannah Lee, Justin R Hamilton
Mar 26, 2016·Biochemical and Biophysical Research Communications·Rui-Qing HePing-Jin Gao
Jun 10, 2018·British Journal of Pharmacology·Philip Wenzel
Mar 9, 2005·American Journal of Physiology. Renal Physiology·Dinesh M Shah
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