Protective effect of the K+ channel opener KRN4884 on peripheral occlusive arterial disease in rats.
1. The effect of the potassium channel opener KRN4884 on the peripheral arterial occlusion model induced by laurate was examined and compared with that of beraprost sodium and nilvadipine. 2. KRN4884 or beraprost sodium prevented macroscopic changes in the paw after the injection of laurate. In contrast, nilvadipine did not improve the lesions. 3. KRN4884 produced a dose-dependent increase in gastrocnemius blood flow in the chronic femoral artery-ligated rats. The effect of KRN4884 on the blood flow was stronger in the hypoxic muscle than in the normal muscle. 4. KRN4884 did not have a direct antiplatelet aggregation activity. 5. These findings suggest that KRN4884 is useful for the therapy of peripheral arterial occlusive disease and that the effect of KRN4884 is associated with an increase in blood flow in ischemic skeletal muscle.
Yoshino
T
T
Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., Gunma, Japan.
Ohta
H
H
Jinno
Y
Y
Torii
Y
Y
Ogawa
N
N
Izawa
T
T
Okada
Y
Y
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000517:prevention & control*; D001162:Arteriosclerosis Obliterans / Q000188:drug therapy*; D003250:Constriction; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005263:Femoral Artery; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013919:Thromboangiitis Obliterans / Q000188:drug therapy*
C096484:KRN 4884; D015221:Potassium Channels; D011725:Pyridines; C048081:beraprost; D011464:Epoprostenol