Effect of spironolactone and captopril on nitric oxide and S-nitrosothiol formation in kidney of L-NAME-treated rats

Although angiotensin-converting enzyme (ACE) inhibitors are well-established drugs in the treatment of hypertension, they are not supposed to be sufficient in the inhibition of aldosterone formation. The present study analyzes the effect of aldosterone receptor antagonist, spironolactone and ACE inh...

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Bibliographic Details
Published in:Kidney international 2006-07, Vol.70 (1), p.170-176
Main Authors: Pechanova, O., Matuskova, J., Capikova, D., Jendekova, L., Paulis, L., Simko, F.
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals
Antihypertensive Agents - pharmacology
Antihypertensive Agents - therapeutic use
Biological and medical sciences
Blood Pressure - drug effects
captopril
Captopril - pharmacology
Captopril - therapeutic use
Enzyme Inhibitors
hypertension
Hypertension, Renal - chemically induced
Hypertension, Renal - enzymology
Hypertension, Renal - prevention & control
kidney
Kidney - chemistry
Kidney - drug effects
Kidney - metabolism
Male
Medical sciences
Mineralocorticoid Receptor Antagonists - pharmacology
Mineralocorticoid Receptor Antagonists - therapeutic use
Nephrology. Urinary tract diseases
NG-Nitroarginine Methyl Ester
Nitric Oxide - analysis
Nitric Oxide - biosynthesis
Nitric Oxide Synthase Type III - analysis
Nitric Oxide Synthase Type III - metabolism
NO synthase
Rats
Rats, Wistar
S-nitrosothiols
S-Nitrosothiols - analysis
S-Nitrosothiols - metabolism
spironolactone
Spironolactone - pharmacology
Spironolactone - therapeutic use
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Summary:Although angiotensin-converting enzyme (ACE) inhibitors are well-established drugs in the treatment of hypertension, they are not supposed to be sufficient in the inhibition of aldosterone formation. The present study analyzes the effect of aldosterone receptor antagonist, spironolactone and ACE inhibitor, captopril on nitric oxide (NO) and S-nitrosothiol formation in the kidney of NG-nitro-L-arginine methyl ester (L-NAME)-treated rats. Male Wistar rats were divided into six groups: (1) controls, (2) L-NAME (40 mg/kg/day), (3) spironolactone (200 mg/kg/day), (4) captopril (100 mg/kg/day), (5) L-NAME+spironolactone, and (6) L-NAME+captopril. After 4 weeks, NO synthase (NOS) activity, protein expression of endothelial NOS, inducible NOS and concentration of thiol and S-nitrosothiol groups were determined in the kidney. Besides the increase in systolic blood pressure (by 32%) and the decrease in NOS activity (by 37%), L-NAME treatment lowered the concentration of thiols (by 32%) and S-nitrosothiols (by 36%) in the renal tissue. Simultaneous treatment with spironolactone preserved NOS activity and S-nitrosothiols on the control level, whereas captopril did not affect these parameters modified by L-NAME treatment. Moreover, spironolactone increased expression of endothelial NOS protein without affecting inducible NOS protein expression. In conclusion, both captopril and spironolactone prevented L-NAME-induced hypertension and the decline of the antioxidant potential of the kidney tissue. However, only spironolactone improved NOS activity which led to the S-nitrosothiols formation. Both NO itself and S-nitrosothiols may contribute to the preventive effect of spironolactone against development of L-NAME-induced hypertension.
ISSN:0085-2538
1523-1755
DOI:10.1038/sj.ki.5001513