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Angiotensin II type 1 receptor blockade prevents up-regulation of angiotensin II type 1A receptors in rat injured artery.

Authors: Tazawa, S  Nakane, T  Chiba, S 
Citation: Tazawa S, etal., J Pharmacol Exp Ther. 1999 Feb;288(2):898-904.
Pubmed: (View Article at PubMed) PMID:9918604

We investigated the effects of the angiotensin II (Ang II) type 1 receptor (AT1) antagonist KRH-594 on levels of the mRNAs for AT1A, AT1B, platelet-derived growth factor-receptor beta (PDGF-Rbeta), and extracellular matrix (ECM)-related genes using the competitive reverse transcription-polymerase chain reaction (RT-PCR) method and on neointimal formation in the balloon-injured rat carotid artery. The mRNA levels for AT1A and PDGF-Rbeta, but not for AT1B, increased from day 3 after injury to day 14. KRH-594 administered orally at 3 and 10 mg/kg/day significantly suppressed these increases. KRH-594 (10 mg/kg/day) also suppressed the injury-induced gene expressions for transforming growth factor-beta1 and fibronectin and reduced collagen alpha1(I) and alpha1(III) mRNA levels for the first 7 days after injury. KRH-594 (10 and 30 mg/kg/day) significantly and dose-dependently reduced the neointimal area in cross sections of the artery 14 days after injury. Another AT1 antagonist, TCV-116 (candesartan cilexetil; 1 and 3 mg/kg/day p.o.), had similar effects on the morphological change and AT1A mRNA level, whereas a smooth muscle relaxant, hydralazine (10 mg/kg/day p.o.), did not. These results indicate that up-regulation of AT1A, PDGF-Rbeta, and ECM-related genes in the balloon-injured carotid artery is in part an AT1-mediated phenomenon and that prevention of receptor up-regulation may contribute to the attenuating effects of AT1 antagonists on neointimal formation after injury.

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CRRD Object Information
CRRD ID: 10047106
Created: 2015-07-09
Species: All species
Last Modified: 2015-07-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.