Rho-kinase inhibitor and nicotinamide adenine dinucleotide phosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
Thus, inhibition of Rho-kinase and NADPH oxidase activities may prevent the above smoking-induced impairment of endothelium-dependent vasodilation.
Iida
Hiroki
H
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu-City, Japan. iida@gifu-u.ac.jp
Iida
Mami
M
Takenaka
Motoyasu
M
Fukuoka
Naokazu
N
Dohi
Shuji
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use; D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D000098:Acetophenones; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C056165:acetovanillone; D019255:NADPH Oxidases; D054460:rho-Associated Kinases; D000109:Acetylcholine; C049347:fasudil