Effect of acute thromboxane A2 inhibition on the renal hemodynamics in a spontaneously non-insulin-dependent diabetic rat, Otsuka Long-Evans Tokushima Fatty rat.
Thromboxane (TX) A2 plays important roles on renal injuries in streptozotocin (STZ)-induced diabetic rats, whereas its role on the renal injuries in non-insulin-dependent diabetic (NIDDM) rats remains unknown. We evaluated the effects of an intravenous infusion of TXA2 synthetase inhibitor (OKY-046, 6 mg/kg/h) on the clearances on inulin and para-aminohippurate (Cin, C(PAH)) in a spontaneously NIDDM rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 8), and Long-Evans Tokushima Otsuka (LETO) rats (n = 7), served as control rats, at the age of 40-44 weeks. OLETF rats showed obesity, moderate hyperglycemia, and hyperinsulinemia. Urinary excretion of TXB2 was slightly higher and the ratio of TXB2 to 6-keto prostaglandin F1alpha (6-kPG) was significantly higher in OLETF rats (TXB2/6-kPG: 0.22 +/- 0.04 versus 0.12 +/- 0.02, P < 0.05). Both Cin and C(PAH) were significantly higher in OLETF rats than in LETO rats (Cin: 1.1 +/- 0.1 versus 0.7 +/- 0.1 mL/min/100 g BW, C(PAH): 3.1 +/- 0.2 versus 2.3 +/- 0.3 mL/min/100gBW, P < 0.01). OKY-046 did not restore Cin and C(PAH) in OLETF rats although it significantly decreased urinary excretion of TXB2, and thus ameliorated TXB2/6-kPG in OLETF rats. These data suggested that TXA2 was not involved in the renal hyperfiltration in OLETF rats at the age of 40-44 weeks, and that TXA2 might contribute to renal injuries in OLETF rats through mechanisms other than hemodynamic injury.
Uriu
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Kidney Center and First Department of Internal Medicine, University of Occupational and Enviromental Health School of Medicine, Fukuoka, Japan.
Kaizu
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Qie
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Kai
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Eto
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D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance
D015121:6-Ketoprostaglandin F1 alpha; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D008689:Methacrylates; D013928:Thromboxane A2; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C034364:ozagrel