Apocynin ameliorates pressure overload-induced cardiac remodeling by inhibiting oxidative stress and apoptosis.

Oxidative stress plays an important role in pressure overload-induced 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 angiotensin 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.

Hydrogen sulphide induces vasoconstriction of rat coronary artery via activation of Ca(2+) influx.

AIM: Hydrogen sulphide (H2S) exhibits a dual modulation of isolated artery tension. This study investigated the vasoconstrictive effect of sulphur sodium hydride (NaHS), a donor of gaseous H2S, on rat coronary artery. METHODS: The contractile response of isolated arteries was recorded using a wire myograph. Fluo-3/AM was used to load vascular smooth muscle, and intracellular calcium was determined using confocal laser microscopy. The protein expression of Rho kinase was examined using Western blot. RESULTS: NaHS induced concentration-dependent contractions of rat coronary artery, and the contraction reached approx. 65% of 60 mm KCl-induced contraction. The NaHS-induced contraction was elevated following the removal of endothelium or the use of the nitric oxide synthase inhibitor L-NAME. The cyclooxygenase inhibitor indomethacin reduced NaHS-induced contraction. The Rho kinase inhibitor Y-27632 significantly attenuated NaHS-induced vasoconstriction. Furthermore, NaHS elevated the protein expression of Rho kinase. NaHS-induced contraction was completely abolished in a Ca(2+)-free solution and suppressed by the Ca(2+) influx blocker nifedipine (100 nm). NaHS also significantly increased the change rate of Ca(2+) fluorescence intensity. However, treatment with a Cl(-)/HCO(3-) exchanger blocker, K(+) channel blockers, the mitogen-activated protein kinase inhibitor U-0126 or cyclic adenosine monophosphate did not affect contraction. Species-dependent differences in NaHS-induced vasoconstriction were observed because these effects were only modest in dog coronary artery and absent in rabbit coronary artery. CONCLUSIONS: NaHS induces the contraction of rat coronary artery, which is dependent on the activation of Ca(2+) influx. Rho kinase likely participates in the vasoconstriction.

The determination of optimal initial tension in rat coronary artery using wire myography.

The aim of the present study was to determine the optimal initial tension, i.e. initial stretch for rat coronary artery when using the multi-wire myograph system. We used the normalization procedure to mimic physiological conditions and to stretch the coronary arterial segments to normalized internal circumference (IC(1)). It is determined the internal circumference when the vessel relaxed under a transmural pressure of 100 mm Hg (IC(100)), and the IC(1) is calculated by multiplying the IC(100) by a factor k. The impact of different factor k on the initial stretch and agonist-induced tension of coronary arteries were investigated. The results showed that the maximal agonist-induced tension was achieved at the factor k value of 0.90 and the initial stretch tension was given 1.16+/-0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most appropriate initial tension was 1.16-1.52 mN/mm. The equilibration time of the coronary artery segments should be at least 1.0 h. In the same optimal initial tension, the agonist-induced tension increased as equilibration time lengthened.