Vascular thrombin receptor regulation in hypertensive rats

Quinn Capers IV, Jørn Bech Laursen, Toshiki Fukui, Sanjay Rajagopalan, Ichiro Mori, Pingping Lou, Brace A. Freeman, William R. Berrington, Kathy K. Griendling, David G. Harrison, Marschall S. Runge, R. Wayne Alexander, W. Robert Taylor

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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 thromhin 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 thrombininduced constriction in isolated endothelium- denuded aortic rings. The AT(1) 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 smooth muscle of rats treated with Ang II represents a novel in vivo mechanism through which the hypertensive effects of Ang II are mediated.

Original languageEnglish (US)
Pages (from-to)838-844
Number of pages7
JournalCirculation research
Volume80
Issue number6
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • angiotensin II
  • aorta
  • Dahl rat
  • hypertension
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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