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

• Published in: Journal of the renin-angiotensin-aldosterone system 2008-06, Vol.9 (2), p.89-94
• Main Authors: Iida, Hiroki, Iida, Mami, Takenaka, Motoyasu, Fukuoka, Naokazu, Dohi, Shuji
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use; Acetophenones - pharmacology; Acetophenones - therapeutic use; Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Animals; Arterioles - drug effects; Cerebrovascular Circulation - drug effects; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Enzyme Inhibitors - therapeutic use; Male; NADPH Oxidases - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - antagonists & inhibitors; Smoking - physiopathology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use
• ISSN: 1470-3203; 1752-8976
• DOI: 10.3317/jraas.2008.012

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.