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Rho-kinase inhibitor and Nicotinamide Adenine Dinucleotide PHosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats

Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu-City, Japan, iida{at}gifu-u.ac.jp

Mami Iida

2nd Department of Internal Medicine (Cardiology) and Anesthesiology, Gifu University Graduate School of Medicine, Gifu-City, Japan

Motoyasu Takenaka

Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu-City, Japan

Naokazu Fukuoka

Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu-City, Japan

Shuji Dohi

Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu-City, Japan

Introduction. We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral vessels, and that blocking the angiotensin II (Ang II) type 1 (AT1) receptor with valsartan prevented this impairment. Our aim was to investigate the effects of a Rho-kinase inhibitor (fasudil) and a Nicotinamide Adenine Dinucleotide PHosphate (NADPH) oxidase inhibitor (apocynin) on smoking-induced endothelial dysfunction in cerebral arterioles.

Method. In Sprague—Dawley rats, we used a closed cranial window preparation to measure changes in pial vessel diameters following topical acetylcholine (ACh) before smoking. After one-minute smoking, we again examined the arteriolar responses to ACh. Finally, after intravenous fasudil or apocynin pre-treatment we re-examined the vasodilator responses to topical ACh (before and after cigarette smoking).

Results. Under control conditions, cerebral arterioles were dose-dependently dilated by topical ACh (10^-6 M and 10^-5 M). One hour after a one-minute smoking (1 mg-nicotine cigarette), 10^-5 M ACh constricted cerebral arterioles. However, one hour after a one-minute smoking, 10^-5 M ACh dilated cerebral pial arteries both in the fasudil pre-treatment and the apocynin pre-treatment groups, responses that were significantly different from those obtained without fasudil or apocynin pre-treatment.

Conclusion. Thus, inhibition of Rho-kinase and NADPH oxidase activities may prevent the above smoking-induced impairment of endothelium-dependent vasodilation.

Key Words: cerebral microcirculation • endothelial dysfunction • NADPH-oxidase inhibitor • oxidative stress • rat • renin-angiotensin system • Rho-kinase inhibitor • smoking

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 9, No. 2, 89-94 (2008)
DOI: 10.3317/jraas.2008.012


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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 Iida, H. Articles by Dohi, S. Search for Related Content PubMed PubMed Citation Articles by Iida, H. Articles by Dohi, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Smoking Social Bookmarking                         What's this?