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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

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


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