Abstract | BACKGROUND: METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats were transplanted orthotopically into fully major histocompatibility complex mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were harvested and examined histologically, and the concentration of eicosanoids in the grafts were analyzed. RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis, which involved gradual intimal thickening and medial thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial inflammation. Although inhibition of medial thinning or a decrease in medial nuclear density was not observed, OKY-046 administration alone significantly inhibited an increase in intimal thickness. OP-2507 administration alone significantly inhibited a decrease in medial nuclear density and intimal thickening. Combined treatment with OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio of thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic rejection.
|
Authors | T Hirano, Y Nakafusa, R Kawano, K Motoyama, T Arima, A Sugitani, M Tanaka |
Journal | Surgery
(Surgery)
Vol. 129
Issue 5
Pg. 595-605
(May 2001)
ISSN: 0039-6060 [Print] United States |
PMID | 11331452
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Enzyme Inhibitors
- Methacrylates
- Superoxides
- Thromboxane A2
- 6-Ketoprostaglandin F1 alpha
- OP 2507
- Epoprostenol
- Thromboxane-A Synthase
- ozagrel
|
Topics |
- 6-Ketoprostaglandin F1 alpha
(metabolism)
- Animals
- Aorta
(pathology, transplantation)
- Arteriosclerosis
(drug therapy, enzymology, prevention & control)
- Cell Nucleus
(pathology)
- Drug Therapy, Combination
- Enzyme Inhibitors
(pharmacology)
- Epoprostenol
(analogs & derivatives, pharmacology)
- Kinetics
- Male
- Methacrylates
(pharmacology)
- Rats
- Rats, Inbred Lew
- Rats, Wistar
- Superoxides
(metabolism)
- Thromboxane A2
(metabolism)
- Thromboxane-A Synthase
(antagonists & inhibitors)
- Transplantation, Homologous
|