Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats.
OBJECTIVE
To examine whether iNOS contributes to endothelial dysfunction in aged rats.


METHODS
Male Sprague Dawley rats were divided into three groups: young rats, aged rats treated with vehicle and aged rats treated with N-[3-(Aminomethyl) benzyl] acetamidine (1400W, 1 mg/kg, ip). Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot. Nitrotyrosine (a marker for peroxynitrite formation) content and expression in thoracic aortic tissue were determined using enzyme linked immunosorbent assay and immunohistochemistry.


RESULTS
Maximal relaxation induced by acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) in the aged rats treated with vehicle was significantly decreased (70%±15%, P<0.01), as compared with the young rats (95%±8%). However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups. Moreover, iNOS and nitrotyrosine expression increased in the vessels of the aged rats. In the aged rats treated with 1400W (a highly selective iNOS inhibitor) nitrotyrosine expression was reduced and acetylcholine-induced vasorelaxation was markedly improved (maximal relaxation was increased to 87%±8%, P<0.05), but the acidified NaNO₂-induced vasorelaxation had no significant change.


CONCLUSIONS
Our study demonstrated that inhibition of iNOS by 1400W increased endothelium-dependent vasodilation in aged rats. The mechanism was related with attenuation of peroxynitrite formation.
Tian
Jue
J
Department of Physiology, Shanxi Medical University, Taiyuan, China.
Yan
Zi
Z
Wu
Ye
Y
Zhang
Su-li
SL
Wang
Ke
K
Ma
Xiu-rui
XR
Guo
Li
L
Wang
Jin
J
Zuo
Lin
L
Liu
Jing-yi
JY
Quan
Lin
L
Liu
Hui-rong
HR
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001596:Benzylamines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000578:Amidines; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000109:Acetylcholine