Acute and chronic effects of thromboxane A2 inhibition on the renal hemodynamics in streptozotocin-induced diabetic rats. 1994

K Uriu, and K Kaizu, and O Hashimoto, and N Komine, and S Etoh
Kidney Center, University of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan.

We examined acute and chronic effects of thromboxane (TX) A2 inhibition on the renal hemodynamics at early and late stage of untreated streptozotocin (STZ)-induced diabetic rats. Two weeks and 28 weeks after the induction of diabetes, renal blood flow (RBF) under anesthesia was measured with an electromagnetic flowmeter before and after TXA2 inhibition. In two-week-old diabetic rats, a specific TXA2 synthetase inhibitor, OKY-046, or a specific TXA2 receptor antagonist, Sulotroban, increased renal vascular resistance (RVR) and ameliorated the hyperperfusion. The renal vasoconstrictive effect of OKY-046 was blunted by an angiotensin converting enzyme (ACE) inhibitor, MK422, or an angiotensin II receptor antagonist, Saralasin. On the contrary, OKY-046 ameliorated the renal hypoperfusion by decreasing RVR in 28-week-old diabetic rats. Chronic oral administration of OKY-046 ameliorated not only the renal hyperperfusion but increased urinary albumin excretion (UAE) at two weeks, but also the renal hypoperfusion, filtration fraction and UAE at 24 weeks. It is suggested that TXA2 might, at least in part, play important roles in the hyperperfusion by modulating activity of the renin-angiotensin system at an early stage of untreated diabetic rats and in the hypoperfusion at the late stage of untreated diabetic rats, and that TXA2 is also involved in the increase of UAE. These results support roles for TXA2 in the progression of renal injury in STZ-induced diabetic rats.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
D012079 Renal Circulation The circulation of the BLOOD through the vessels of the KIDNEY. Kidney Circulation,Renal Blood Flow,Circulation, Kidney,Circulation, Renal,Blood Flow, Renal,Flow, Renal Blood
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000806 Angiotensin-Converting Enzyme Inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. ACE Inhibitor,ACE Inhibitors,Angiotensin Converting Enzyme Inhibitor,Angiotensin I-Converting Enzyme Inhibitor,Angiotensin-Converting Enzyme Inhibitor,Kininase II Inhibitor,Kininase II Inhibitors,Angiotensin I-Converting Enzyme Inhibitors,Angiotensin-Converting Enzyme Antagonists,Antagonists, Angiotensin-Converting Enzyme,Antagonists, Kininase II,Inhibitors, ACE,Inhibitors, Angiotensin-Converting Enzyme,Inhibitors, Kininase II,Kininase II Antagonists,Angiotensin Converting Enzyme Antagonists,Angiotensin Converting Enzyme Inhibitors,Angiotensin I Converting Enzyme Inhibitor,Angiotensin I Converting Enzyme Inhibitors,Antagonists, Angiotensin Converting Enzyme,Enzyme Antagonists, Angiotensin-Converting,Enzyme Inhibitor, Angiotensin-Converting,Enzyme Inhibitors, Angiotensin-Converting,II Inhibitor, Kininase,Inhibitor, ACE,Inhibitor, Angiotensin-Converting Enzyme,Inhibitor, Kininase II,Inhibitors, Angiotensin Converting Enzyme
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013311 Streptozocin An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. Streptozotocin,2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose,Streptozotocine,Zanosar
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide

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