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Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat
T M Kennefick1, T T Oyama, M M Thompson
1Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland, USA.
Abstract:
The renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. In diabetes, renal RAS components are dysregulated, potentially increasing renal RAS effects. To explore the renal RAS, studies were conducted in control and diabetic rats. In both groups, intravenous angiotensin (ANG) I and ANG II produced similar increases in mean arterial pressure (MAP). In contrast, glomerular filtration rate defined only in diabetic rats. Renal plasma flow fell in both groups but decreased more in diabetic rats. Additional groups were given the same dose of ANG I directly into the left renal artery, and hemodynamics were studied in the treated and untreated kidneys. In contrast to the intravenous studies, intra-arterial ANG I had no effect on MAP in either group. The renal hemodynamic effects were similar to those in intravenous studies. Additionally, diabetic rats exhibited enhanced hemodynamic sensitivity in the untreated kidney, suggesting that renal effects could occur at nonpressor concentrations of circulating ANG II. Thus renal (but not systemic) responsiveness to angiotensins is enhanced in diabetic rats.
Insights
Diabetic rats show heightened kidney sensitivity to the renin-angiotensin system (RAS) and its components, like angiotensin II. This enhanced renal responsiveness, distinct from systemic effects, may contribute to diabetic nephropathy progression.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Physiology
Background:
- The renin-angiotensin system (RAS) plays a key role in diabetic nephropathy pathogenesis.
- Dysregulation of renal RAS components in diabetes can amplify its effects.
- Understanding localized renal RAS activity is crucial for managing diabetic kidney disease.
Purpose of the Study:
- To investigate the specific effects of the RAS on renal hemodynamics in diabetic rats.
- To compare systemic versus intra-renal responses to angiotensin I and II in diabetic and control states.
- To determine if diabetic rats exhibit altered hemodynamic sensitivity to angiotensins within the kidney.
Main Methods:
- Comparative hemodynamic studies in control and diabetic rat models.
- Administration of angiotensin I and II intravenously and intra-arterially.
- Measurement of mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal plasma flow (RPF).
- Assessment of renal hemodynamic responses in both treated and untreated kidneys.
Main Results:
- Intravenous angiotensin I and II increased MAP similarly in both groups.
- Glomerular filtration rate decreased only in diabetic rats.
- Renal plasma flow decreased in both groups, with a greater reduction in diabetic rats.
- Intra-arterial angiotensin I did not affect MAP but induced similar renal hemodynamic changes as intravenous administration.
- Diabetic rats showed enhanced hemodynamic sensitivity in the untreated kidney, indicating localized renal effects.
Conclusions:
- Renal responsiveness to angiotensins is significantly enhanced in diabetic rats compared to systemic responsiveness.
- These localized renal effects may occur even at non-pressor concentrations of circulating angiotensin II.
- The findings highlight a critical role for intra-renal RAS modulation in diabetic nephropathy.