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Endothelin antagonists improve renal function in spontaneously hypertensive rats
T Kato1, S Kassab, F C Wilkins
1Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Hypertension (Dallas, Tex. : 1979)
|April 1, 1995
Summary
Endothelin receptor blockade in spontaneously hypertensive rats (SHR) improved kidney function, increasing renal plasma flow and glomerular filtration rate. This suggests endothelin plays a key role in the renal abnormalities seen in hypertension.
Area of Science:
- Nephrology
- Cardiovascular Research
- Pharmacology
Background:
- Hypertension in spontaneously hypertensive rats (SHR) is linked to impaired renal excretory function, reduced renal plasma flow, and decreased glomerular filtration rate.
- The precise mechanisms underlying these renal functional abnormalities in SHR remain unclear.
- Intrarenal endothelin's role in modulating renal hemodynamics and excretory function in SHR requires investigation.
Purpose of the Study:
- To elucidate the role of intrarenal endothelin in altering renal hemodynamic and excretory function in spontaneously hypertensive rats (SHR).
- To investigate the effects of endothelin receptor antagonists on renal function in SHR compared to Wistar-Kyoto rats (WKY).
Main Methods:
- Infusion of endothelin receptor antagonists (PD 145065 and FR 139317) or saline into the renal interstitium of SHR and WKY rats.
- Measurement of renal perfusion pressure, glomerular filtration rate, renal plasma flow, and renal interstitial hydrostatic pressure.
- Assessment of urine flow and sodium excretion parameters.
Main Results:
- Intrarenal infusion of endothelin receptor antagonists significantly increased glomerular filtration rate (22%), renal plasma flow (37%), and renal interstitial hydrostatic pressure in SHR.
- These hemodynamic improvements were accompanied by enhanced urine flow and sodium excretion in SHR.
- Endothelin receptor blockade did not affect renal function in normotensive WKY rats, indicating a specific role in the hypertensive model.
Conclusions:
- Intrarenal endothelin receptor blockade effectively improves renal hemodynamic and excretory function in spontaneously hypertensive rats (SHR).
- These findings highlight endothelin's contribution to renal dysfunction in hypertension and suggest therapeutic potential for endothelin receptor antagonists.