Pharmacologic inhibition of nitric oxide synthases and cyclooxygenases enhances intimal hyperplasia in balloon-injured rat carotid arteries

Journal of Vascular Surgery
Jens W FischerAlexander W Clowes

Abstract

Extensive proliferation and migration of smooth muscle cells (SMCs) contribute to development of fibromuscular intimal hyperplasia in response to balloon catheter-induced injury of the left carotid artery in Fischer 344 rats. The purpose of the present study was to test the hypothesis that endogenously generated nitric oxide (NO) and prostaglandins act synergistically to limit the extent of neointimal hyperplasia. The left carotid artery of Fischer 344 rats was injured with a 2F balloon catheter. The following treatment was initiated 24 hours before arterial injury, and was continued for 2 weeks: N-nitro-l-arginine (L-NA; 10 mg/kg/d, in drinking water), indomethacin (1.5 mg/kg/d per gavage), and L-NA (10 mg/kg/d) plus indomethacin (1.5 mg/kg/d). After application of an overdose of pentobarbital animals were formalin-fixed. Subsequently, paraffin-embedded cross sections of the uninjured and injured carotid arteries were analyzed morphometrically. SMC proliferation was determined by incorporation of 5-bromo-2'-deoxyuridine. Two weeks after injury, L-NA caused a 1.29-fold +/- 0.29-fold (mean +/- SD; n = 14; P <.05) increase in the intima-media ratio, compared with control animals, whereas indomethacin had no effect. Combined treat...Continue Reading

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Citations

Nov 12, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Melvin E KlegermanDavid D McPherson
Aug 8, 2009·Journal of the American College of Cardiology·Shao-Ling HuangDavid D McPherson
Aug 8, 2007·Journal of Vascular Surgery·Sadaf S AhanchiMelina R Kibbe
May 9, 2012·Nitric Oxide : Biology and Chemistry·Nick D TsihlisMelina R Kibbe
Feb 4, 2014·Journal of Molecular and Cellular Cardiology·Sami A Omar, Andrew James Webb
Aug 24, 2007·The Journal of Surgical Research·Francesco OnoratiAttilio Renzulli
Dec 4, 2012·Circulation·Lihong ChenGarret A FitzGerald
Dec 6, 2017·PloS One·Wiwat ChancharoenthanaSomchai Eiam-Ong
Jun 9, 2021·The Journal of Pharmacology and Experimental Therapeutics·Keivan GolshiriAnton J M Roks

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