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

Abstract

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.

Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB

“…Since several studies have shown the role of ANGII in the beneficial effect of captopril in arterial hypertension [30,49], more studies were designed in order to understand the mechanisms involved in the anti-inflammatory properties of captopril in the left ventricle of SHR. Our results indicate that captopril might act via interfering with NF-kB pathway activation, most probably by blocking the ANGII II production in the left ventricle of hypertensive animals.…”

“…Thus, captopril has been proved to be beneficial in experimental autoimmune encephalomyelitis [25], adriamycin-induced nephropathy [26], arthritis [27] and experimental rat colitis [28]. Captopril suppresses the inflammation in endotoxin-induced uveitis in rats [29]; improves oxidative stress in the kidney of L-NAME-treated rats [30], and increases the antioxidant defenses in mouse tissues [31]. In addition, the treatment with captopril produces a decrease in the left ventricle inflammatory cell infiltration in angiotensin II and aldosterone-salt-induced hypertension [32].…”

Detection of S-nitrosothiols in biological fluids: A comparison among the most widely applied methodologies

“…The analytical difficulties are mirrored by the incontrovertible observation that reported values by different research groups cover some orders of magnitude also when analyzing the same tissue or biological fluid. It is wondering that one research group found 20-30 nmol/mg PSNO (i.e., 1.5-2 mM) in endothelial cells [38] or rat kidney [39], a value that corresponds to the levels of cellular glutathione (GSH) itself. Conversely, Bryan et al [40] found only 10-100 nM of RSNOs in almost all the analyzed tissues.…”

Combination Therapy With Telmisartan and Spironolactone Alleviates L-NAME Exacerbated Nephrosclerosis With an Increase in PPAR-.GAMMA. and Decrease in TGF-.BETA.1

“…The doses of spironolactone and telmisartan were selected based on earlier reports so that they would exhibit comparable antihypertensive effects. [15][16][17] During the final week of treatment, all rats were placed in metabolic cages for 2 days to measure 24-hour urinary excretions of creatinine, protein, and nitric oxides (NOx). Plasma and urinary creatinine levels were assayed by enzymatic colorimetry and urinary NOx levels were determined by high performance liquid chromatography.…”