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Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade

95 Postgraduate, Hubei Medical, University, 39 Donghu Road, Wuhan 430071 China, Hospital of Huben Medical University, Wuhan, 430071 China

Wang Yui Ying

95 postgraduate, Hubei Medical University, 39 Donghu Road, Wuhan 430071 China

Ren Jang Hua

Yale Y Ji

95 postgraduate, Hubei Medical University, 39 Donghu Road, Wuhan 430071 China, yale_yayou.j@ pharma.novartis.com

Marc de Gasparo

Novartis Pharma AG, Metabolic, Cardiovascular and Endocrine Therapeutic Area, 4002 Basel Switzerland

The effects of the specific angiotensin II (Ang II) AT₁receptor blocker valsartan on events related to restenosis were investigated in rabbits after common carotid balloon injury. Six animals were given valsartan from two days prior to injury until 14 days post-injury. Three control groups (n=6 in each group) were either sham-operated, untreated or treated with the angiotensin-converting enzyme (ACE) inhibitor, captopril. Both ACE inhibition and AT₁-receptor blockade had marked effects on plasma levels of endothelin ET₁, thromboxane TXB₂ and 6-keto-PGF1-alpha. The most dramatic effects on ET₁ levels were seen in rabbits treated with valsartan, where levels were reduced to values close to those for sham-operated animals (96.85 vs. 86.45 pg/ml). Captopril treatment led to a statistically significant (p<0.01) reduction in ET₁ levels compared with untreated animals, but the reduction was only about half that seen with AT₁receptor blockade. TXB₂ levels doubled (202.58 vs. 413.28 pg/ml) upon arterial injury in control animals but rose by only 20—35% in rabbits treated with captopril (246.45 pg/ml) or valsartan (268.13). In untreated animals, 6-keto-PGF₁-alpha levels decreased slightly after injury, but for both the captopril and valsartan groups, there were significant increases in levels of this prostaglandin derivative, effects attributed to the action of bradykinins. Levels were highest in the captopril-treated animals. Valsartan and captopril treatment led to a significant reduction in neointimal thickness and the extent of lumen stenosis compared with untreated animals. Both treatments were effective in reducing neointimal area and significantly (p<0.05) reduced cell proliferation. The differences between treatments can be attributed to the different actions of the agents, as valsartan leaves the AT₂-receptor unblocked, while captopril, through inhibition of Ang II synthesis, prevents stimulation of both receptors. A combination of both treatments may be a possible way forward in the clinical prevention of restenosis.

Key Words: restenosis • endothelin • angiotensin-receptor blockade • valsartan • bradykinins

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1, 19-24 (2001)
DOI: 10.3317/jraas.2001.003


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Tong Chuang Feng Articles by de Gasparo, M. Search for Related Content PubMed PubMed Citation Articles by Tong Chuang Feng, Articles by de Gasparo, M. Social Bookmarking                         What's this?