Oxidative stress plays an important role in pressure overloadinduced
cardiac remodeling. The purpose of this study was to determine whether apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, attenuates pressure overload-induced cardiac remodeling in rats. After abdominal aorta constriction, the surviving rats were randomly divided into four groups: sham group, abdominal aorta constriction group, apocynin group, captopril group. Left ventricular pathological changes were studied using Masson’s trichrome staining. Metalloproteinase-2 (MMP-2) levels in the left ventricle were analyzed by western blot and gelatin zymography. Oxidative stress and apoptotic index were also examined in cardiomyocytes using dihydroethidium and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), respectively. Our results showed that abdominal aorta constriction significantly caused excess collagen deposition and cardiac insult. Treatment with apocynin significantly inhibited deposition of collagen and reduced the level of MMP-2. Furthermore, apocynin also decreased the NADPH oxidase activity, reactive oxygen species production and cardiomyocyte apoptotic index. Interestingly, apocynin only inhibited NADPH oxidase activity without affecting its expression or the level of angiotension II in the left ventricle. In conclusion, apocynin reduced collagen deposition, oxidative stress, and inhibited apoptosis, ultimately ameliorating cardiac remodeling by mechanisms that are independent of the renin-angiotensin system.
L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine-induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5 mg/ml p.o.), L-arginine + apocynin (2.5 mmol/l p.o.), L-arginine + catalase (10000 U/kg/day i.p.) and L-arginine plus apocynin + catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs. 91±2 mmHg) and heart rate (298±21 vs. 254±15 bpm), enhanced urinary output (21.5±4.2 vs. 32±1.9 ml/24 h, increased creatinine clearance (1.72±0.56 vs. 2.62±0.40 ml/min/kg), and fractional sodium excretion (0.88±0.16 vs. 1.18±0.16 %), caused proteinuria (28.10±1.93 vs. 35.26±1.69 mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs. 258±5 bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13 m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by ~51 %, P<0.05) but decreased superoxide dismutase (by ~31 %, P<0.05) and total antioxidant capacity (by ~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine-treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in the states of oxidative stress.