Angiotensin-Converting Enzyme Inhibition Delays Onset of Glucosuria With Regression of Renal Injuries in Genetic Rat Model of Non-Insulin-Dependent Diabetes Mellitus
| Autor: | Atsushi Numabe, Nobuhito Hirawa, Tomoko Gomi, Toshio Ikeda, Masao Omata, Hiroshi Nagoshi, Yoshio Uehara, Atsuo Goto, Yukari Kawabata, Hideyuki Negoro, Satoshi Fujiwara |
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| Rok vydání: | 1998 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Rat model 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Diabetes mellitus Genetic model Renin–angiotensin system medicine Kidney injury Pharmacology (medical) Pharmacology biology business.industry Non insulin dependent diabetes mellitus Angiotensin-converting enzyme medicine.disease 030104 developmental biology Endocrinology chemistry Plasminogen activator inhibitor-1 biology.protein Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Cardiovascular Pharmacology and Therapeutics. 3:327-335 |
| ISSN: | 1940-4034 1074-2484 |
| DOI: | 10.1177/107424849800300408 |
| Popis: | Background: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether angiotensin inhibition influences the onset of NIDDM and brings about a regression of renal injury in diabetes mellitus. Methods and Results: Six-week-old OLETF rats were treated with the angiotensin-con verting enzyme (ACE) inhibitors imidapril or enalapril for 16 weeks. Systolic blood pres sure is increased in an age-dependent manner in OLETF rats. In this study, the elevation in systolic blood pressure was dose-dependently reduced by ACE inhibitor treatment. In OLETF rats, plasma concentrations of insulin and glucose increased and the glucosuria occurred at the age of 22 weeks. Simultaneously, OLETF rats exhibited proteinuria and nodular lesions in glomeruli. The ACE inhibitor treatment almost completely reduced glu cosuria, and also decreased plasma concentrations of insulin and glucose in OLETF rats. ACE inhibitor treatment lessened the proteinuria and attenuated morphologically the severity of nodular lesions in OLETF rats. Moreover, increases in plasminogen activator inhibitor 1 (PAI-1) in OLETF rats were reduced by the ACE inhibitor treatment, and the improvement of glomerular lesions was related to decreases of PAI-1 and angiotensin II levels in plasma but not to improvement of glucose metabolism. Conclusions: ACE inhibitors delay onset of NIDDM with attenuation of kidney injury. The regression of kidney lesions is probably due to angiotensin reduction but not to glucose metabolism per se. ACE inhibitor drug therapy may be useful in preventing NIDDM and the subsequent renal injury in patients with NIDDM. |
| Databáze: | OpenAIRE |
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