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Endothelium-derived relaxing factor modulates renal interstitial cyclic GMP
1Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Journal of Cardiovascular Pharmacology
|January 1, 1992
Summary
This study shows that measuring renal interstitial cyclic guanosine monophosphate (cGMP) is possible in vivo. Inhibition of endothelium-derived relaxing factor (EDRF) with NG-monomethyl-L-arginine (L-NMMA) decreased renal cGMP levels, suggesting EDRF
Area of Science:
- Nephrology
- Physiology
- Pharmacology
Background:
- Endothelium-derived relaxing factor (EDRF) mediates vasodilation via cyclic guanosine monophosphate (cGMP).
- EDRF's labile nature limits its actions to local environments.
- Monitoring renal interstitial cGMP is crucial for understanding local renal function control.
Purpose of the Study:
- To demonstrate the feasibility of monitoring renal interstitial cGMP in vivo.
- To investigate the effect of EDRF inhibition on renal interstitial and urinary cGMP levels.
- To explore the role of EDRF as a renal paracrine substance.
Main Methods:
- Renal interstitial microdialysis technique in anesthetized dogs.
- Intrarenal arterial administration of EDRF inhibitor NG-monomethyl-L-arginine (L-NMMA).
- Measurement of cGMP levels in renal interstitial fluid and urine from both kidneys.
Main Results:
- L-NMMA administration caused a dose-dependent decrease in ipsilateral renal interstitial and urinary cGMP.
- Lower doses of L-NMMA did not affect contralateral renal cGMP levels.
- Higher doses of L-NMMA reduced cGMP in both ipsilateral and contralateral kidneys, indicating systemic effects.
Conclusions:
- The study successfully demonstrates in vivo monitoring of renal interstitial cGMP.
- EDRF inhibition leads to reduced renal cGMP, supporting its role in renal function.
- Findings suggest EDRF acts locally as a paracrine mediator modulating renal interstitial cGMP.