Analysis of hemodynamics and angiogenic response to ischemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Leprfa (SDT fatty) rats.

Peripheral artery disease (PAD) is defined as peripheral blood flow impairment, especially in the legs, caused by atherosclerotic stenosis. The disease decreases quality of life because of intermittent claudication or necrosis of the leg. The hindlimb ischemia model, in which ischemia is induced by femoral artery ligation, is often utilized as a PAD model. In the hindlimb ischemia model, nonmetabolic syndrome animals are mainly used. In this study, we investigated the usefulness of Spontaneously Diabetic Torii Lepr^fa (SDT fatty) rats, a new model for obese type 2 diabetes, as a new PAD animal model. We found that hindlimb blood flow in SDT fatty rats was significantly lower than that in Sprague-Dawley (SD) rats under nonischemic conditions. Furthermore, SDT fatty rats showed a significantly higher plasma nitrogen oxide level, shorter prothrombin time, and shorter activated partial thromboplastin time than SD rats. In addition, we found that the change in blood flow 7 days after induction of hindlimb ischemia and the number of Von Willebrand Factor-positive vessels in gastrocnemius muscles were significantly lower in SDT fatty rats than in SD rats. These results suggest that excess production of reactive oxygen species and coagulation activation could be involved in lower blood flow in nonischemic rats and that decreased angiogenesis could be involved in the poor recovery of blood flow in SDT fatty rats with hindlimb ischemia. Taken together, our results suggest that SDT fatty rats might be useful as a new model for PAD with metabolic syndrome.