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Nitric oxide regulates renal cortical cyclooxygenase-2 expression
H F Cheng1, J L Wang, M Z Zhang
1George M. O'Brien Kidney and Urologic Diseases Center and Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennesee 37232, USA.
American Journal of Physiology. Renal Physiology
|July 15, 2000
Summary
Nitric oxide (NO) regulates cyclooxygenase-2 (COX-2) expression in the kidney, particularly in response to low salt and ACE inhibition. This interaction is crucial for controlling blood vessel tone and the renin-angiotensin system.
Area of Science:
- Nephrology
- Molecular Biology
- Physiology
Background:
- Cyclooxygenase-2 (COX-2) is found in the rat kidney's cortical thick ascending limb (cTALH) and macula densa.
- COX-2 expression increases with low-salt diets or angiotensin-converting enzyme (ACE) inhibition.
- Neuronal nitric oxide synthase (nNOS) is also localized to the macula densa and surrounding cTALH.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in regulating COX-2 expression.
- To understand the interaction between NO and COX-2 systems in renal function.
Main Methods:
- In vivo studies: Rats were subjected to normal diet, low-salt diet, or low-salt diet with captopril (ACE inhibitor).
- nNOS inhibitors (7-nitroinidazole or S-methyl-thiocitrulline) were administered to assess their effect on COX-2 expression.
- In vitro studies: Primary cultures of rabbit cTALH cells were used to examine basal and stimulated COX-2 expression.
Main Results:
- nNOS inhibitors blocked the increase in COX-2 mRNA and protein induced by low salt and ACE inhibition in vivo.
- NO donor (SNAP) and cGMP stimulated basal COX-2 expression in cultured cTALH cells.
- 7-NI inhibited basal COX-2 expression in cultured cells, an effect partially reversed by cGMP.
Conclusions:
- NO mediates increased renal cortical COX-2 expression during volume depletion.
- There are significant interactions between the NO and COX-2 systems in regulating arteriolar tone and the renin-angiotensin system via the macula densa.