| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Experimental and Clinical Endocrinology & Diabetes | ||||
| Publisher: | JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH | ||||
| Place of Publication: | STUTTGART | ||||
| Volume: | 117 | ||||
| Number of Issue or Book Chapter: | 01 | ||||
| Page Range: | pp. 15-20 | ||||
| Date: | 2008 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin II | ||||
| Identification Number: |
| ||||
| Keywords: | SPONTANEOUSLY HYPERTENSIVE-RATS; OBESE ZUCKER RATS; PLASMA-ALDOSTERONE; FATTY RATS; CARDIAC FIBROSIS; NEPHROPATHY; SYSTEM; SALT; SPIRONOLACTONE; HYPERTROPHY; aldosterone; diabetes type 2; rat | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 67557 |
Web of ScienceAbstract
Background: Aldosterone is an important mediator of cardiovascular and renal remodeling. Type II diabetes mellitus leads to renal and cardiac end organ damage. We investigated the renin-angiotensin-aldosterone system in a model of type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling, the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF + ACE-I) and ...
Abstract
Background: Aldosterone is an important mediator of cardiovascular and renal remodeling. Type II diabetes mellitus leads to renal and cardiac end organ damage. We investigated the renin-angiotensin-aldosterone system in a model of type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling, the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF + ACE-I) and its control, the Zucker Lean (ZDL) rat. Methods: Male animals were studied from an age of 7-24 weeks. At ages 7, 14, 17, 20, and 23 weeks, urinary excretion of aldosterone-glucuronide and potassium was assessed. ACE-inhibition with ramipril was started orally at week 13 (1 mg/kg/d). At the end of the study rats were sacrificed and plasma aldosterone concentration and plasma renin activity were measured. Aldosterone synthase (CYP11B2) mRNA expression in the adrenals, kidney, heart and adipose tissue was assessed by real-time PCR. Urinary albumin excretion as marker for diabetic nephropathy was measured in metabolic cages and correlated to aldosterone. Results: Plasma aldosterone concentration and aldosterone-glucuronide was significantly elevated in ZDF rats, and significantly reduced by ACE-inhibiton. In contrast, plasma renin activity was significantly reduced in ZDF rats and normalized by ACE-inhibition. The urinary aldosterone correlated significantly to albuminuria. Adrenal CYP11B2 expression was not significantly higher in ZDF rats. CYP11B2 mRNA was not detected in the kidney, heart and adipose tissue. Conclusion: In ZDF rats, urinary and plasma aldosterone levels were elevated despite reduced plasma renin activity. The reversible effect of ACE-inhibition shows that the up-regulation of aldosterone must be dependent of the renin-angiotensin-system in this type 11 diabetes model. The correlation between aldosterone and diabetic nephropathy suggests a clinical relevance of this observation.
Metadata last modified: 19 Dec 2024 12:13
Altmetric