Endothelium-dependent relaxation by cilostazol, a phosphodiesteras III inhibitor, on rat thoracic aorta.
The relaxation effect of cilostazol, a phosphodiesterase III inhibitor, on the thoracic aorta was investigated. Cilostazol induced the relaxation of the thoracic aorta precontracted by phenylephrine in a concentration-dependent manner. The concentration-dependent relaxation was shifted to the right in the endothelium denuded aorta compared with that of intact endothelium, suggesting that this relaxation was partly dependent on endothelium. Cilostazol-induced relaxation of thoracic aorta tone was reversed by treatment with N(G)-nitro L-arginine (L-NNA), a competitive inhibitor of nitric oxide (NO) synthase. Cilostazol also significantly increased the NO level in the porcine thoracic aorta. In rats treated with cilostazol, the urinary excretion of nitrites, a stable metabolite of NO, and basal production of NO of the aortic ring were significantly greater than in those without treatment. These findings indicate that cilostazol-induced vasodilation of the rat thoracic aorta was dependent on the endothelium, which released NO from aortic endothelial cells.
Nakamura
T
T
Department of Pharmacy, Tokushima University Hospital, Japan.
Houchi
H
H
Minami
A
A
Sakamoto
S
S
Tsuchiya
K
K
Niwa
Y
Y
Minakuchi
K
K
Nakaya
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D000077407:Cilostazol; D046508:Culture Techniques; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000652:urine; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D009573:Nitrites; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D009569:Nitric Oxide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol