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 inhibitor, captopril on nitric oxide (NO) and S-nitrosothiol formation in the kidney of N(G)-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.
Pechanova
O
O
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. olga.pechanova@savba.sk
Matuskova
J
J
Capikova
D
D
Jendekova
L
L
Paulis
L
L
Simko
F
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors; D006977:Hypertension, Renal / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols / Q000032:analysis / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D026403:S-Nitrosothiols; D013148:Spironolactone; D009569:Nitric Oxide; D002216:Captopril; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester