Ramatroban, a TP receptor antagonist, improves vascular responses to acetylcholine in hypercholesterolemic rabbits in vivo.
Recent studies show that 8-iso-prostaglandin F(2alpha), a member of F(2)-isoprostane family, acts as a vasoconstrictor via TP receptor activation; and its local release may contribute to an abnormal vasomotor tone associated with hypercholesterolemia. The purpose of this study was to examine whether ramatroban, a TP receptor antagonist, improves abnormal vascular reactivity in vivo in hypercholesterolemic rabbits. The plasma 8-iso-prostaglandin F(2alpha) levels in hypercholesterolemic groups were significantly higher than those in normal groups. The treatment by ramatroban reversed the attenuation of the vascular response to acetylcholine in hypercholesterolemic groups. However, L-N(G)-nitroarginine methyl ester, a nitric oxide synthase inhibitor, did not inhibit the protective effects of ramatroban. Attenuation of the vascular response to acetylcholine in hypercholesterolemic rabbits was significantly enhanced by 8-iso-prostaglandin F(2alpha). Attenuation of the vascular response to acetylcholine by a cholesterol-rich diet and 8-iso-prostaglandin F(2alpha) was canceled by ramatroban. These findings suggest that ramatroban improves the vascular response in vivo to acetylcholine in hypercholesterolemic rabbits by blocking the action of 8-iso-prostaglandin F(2alpha).
Department of Medical Engineering, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. TIR2@aol.com
Toshiaki
T
Ishizuka
Takemi
T
Matsui
Akira
A
Kurita
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000097:blood / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D002227:Carbazoles; D028441:F2-Isoprostanes; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D000109:Acetylcholine; C063119:ramatroban