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Acute renal effects of endothelin-A blockade: interspecies differences
1Department of Medicine, McGill University, Montreal, Quebec, Canada.
Journal of Cardiovascular Pharmacology
|May 22, 1998
Summary
Acute blockade of endothelin-A (ETA) receptors with LU135252 impairs renal excretory function in rats but not dogs. This interspecies difference highlights varied roles of endothelin in renal regulation.
Area of Science:
- Pharmacology
- Nephrology
- Physiology
Background:
- Endothelin (ET) plays a role in regulating renal function.
- Endothelin-A (ETA) receptors are implicated in renal processes.
- Selective ETA receptor antagonists are potential therapeutic agents.
Purpose of the Study:
- To investigate the acute renal effects of LU135252, a selective ETA receptor antagonist.
- To compare the effects of ETA receptor blockade on renal function in rats and dogs.
Main Methods:
- Conscious rats received i.p. administration of LU135252 (1-10 mg/kg).
- Anesthetized dogs underwent clearance studies with intrarenal LU135252 infusion (0.01-0.1 mg/kg/min).
- Renal excretory function, hemodynamics, and response to volume expansion were assessed.
Main Results:
- In rats, LU135252 significantly decreased diuresis and excretion of sodium and chloride.
- Oral NaCl load excretion was reduced in rats treated with LU135252.
- In dogs, intrarenal LU135252 infusion did not affect renal hemodynamics or excretory function, despite mild blood pressure decrease.
Conclusions:
- Acute ETA receptor blockade impairs renal excretory function in rats, likely at the tubular level.
- Dogs do not exhibit impaired renal excretory function following acute ETA receptor blockade.
- Interspecies differences in ET receptor profile and distribution may explain the varied renal responses.