Effects Of Noise-induced Myocardium Damaged Mediated By Local Cardiac Ang â…¡ And Underlying Mechanisms

OBJECTIVE: Noise pollution has become an increasingly serious problem. Traffic noise,construction noise,community noise have not only disturbed people's normal life, but also affected their health. The World Health Organization has reported cardiovascular disease as the highest cause of mortality. Epidemiological studies suggested that noise affects the cardiovascular system. Noise can increase the blood pressure and electrocardiogram abnormality rate, enve increase the relative risk of ischemic heart disease, which may affect people's health seriously. However, few laboratory-based studied have been done in this area. The exact mechanism of noise-induced cardiovascular disease has not been fully explored. Local cardiac renin-angiotensin system (RAS) is related to a variety of cardiovascular diseases such as myocardial infarction, cardiac hypertrophy, cardiac remolding and heart failure. Studies have suggested that when the local RAS is stimulated, angiotensin II (Ang II) is increased, binds with Ang II receptor (AT), and therefore triggers signal transduction. This causes the enhancement of cardiomyocytes contractility, acceleration of protein synthesis and the rearrangement of cardiomyocytes, eventually leading to cardiomyocyte apoptosis, necrosis, hypertrophy, and remodeling. Research has demonstrated that Ang II can stimulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the primary enzyme to produce reactive oxygen species (ROS) in the cardiovascular system. Studies have also shown that noise exposure can produce ROS in the blood and cochlea. It has not yet been determined whether cardiac RAS mediated any of the effects of noise on heart, or whether ROS derived by RAS mediated the effects of noise on heart. Against this background, we plan to investigate the alteration of cardiac RAS, electrocardiogram, the index of oxidation/antioxidation, the NADPH oxidase subunits and PKC in rat hearts damaged by noise treated with Telmisartan. Based on these changes, this research aims to explore the role of the cardiac RAS in myocardial injury caused by noise exposure and its path of signal transduction, and therefore provide more theoretical and experimental basis for understanding the influence of noise exposure on the cardiovascular system and eventual implications for prevention.METHODS: First, healthy male rats, weighted 140-150g, were exposed to 100dB white niose, 6h/d, 12 wk, building the animal model of heart damaged by noise, according to cardiomyocytes ultrastructure and the oxidative indicies of MDA content and T-AOC in myocardium. And then, radio-immunity method was used to detect the content of Ang II in plasm and myocardium; fluorescent quantitation method of RT-PCR was used to detect the expression of AGT and AT1A mRNA in myocardium. Second, on the basis of this model, ARB was administrated before noise exposure to observe the role of the Ang II, the indicies including myocardiac ultrastructure,electrocardiogram,oxidant/antioxidant, cardiac RAS, expression of NADPH oxidase and PKC. ARB was applied to block the action of Ang II, to explore whether it can reduce noise-induced myocardium impairment and whether oxidative damage caused by noise would be relate to NADPH oxidase, through which to clarify the underlying mechanisms of noise-induced myocardium damaged.RESULTS:1. The hearing of rat was damaged by long term noise exposure with white noise of 100dB, 6h/d, 12 wk, showing the thresholds of ABR increased and peak latency extended.2. Electrocardiogram was changed by long term noise exposure. The HR of noise -exposure group(291.22 bpm) was significantly decreased(p<0.01), comparing with that of the normal control group(379.63 bpm). The duration of P wave, the interval of P-R, and the interval of QRS were extended of the noise-exposure group. The voltage of P wave was raised of the noise-exposure group. The HR of Telmisartan intervention group(291.22 bpm) had the tendency of accelation, but had no significance(p>0.05), comparing with the noise-exposure group. The voltage of P wave was decreased significantly comparing with that of the noise-exposure group.3. Long term noise exposure damaged the myocardium, showing mitochondrial accumulating, swelling, cristae disappearing, even vacuoles happen. The damage of mitochondrial and myocardium were relieved by Telmisartan intervention.4. The O2–and MDA content of myocardium of noise-exposure group were significantly raised(p<0.01, p<0.05), comaring with the normal control group. The SOD activity of noise-exposure group was unsignificantly changed(p>0.05), comparing with the normal control group. The T-AOC of noise-exposure group was significantly decreased(p<0.01), comparing with that of the normal control group. Telmisartan intervention may raise the SOD activity and T-AOC in the myocardium, decrease the O2–and MDA content of myocardium after noise exposure, Which indicating noise exposure can increase ROS generating, damaged antioxidant capability of myocardium, and then lead to myocardium oxidative damaged. Telmisartan can raise the antioxidant capability of myocardium, reduce the oxidative damaged.5. Long term noise exposure can raise the AngⅡcontent of plasma and myocardium(p<0.05,p<0.01), comparing with the normal control group. The expression of AGT mRNA of noise-exposure group had the tendency of augmentation, comparing with the normal control group. The expression of AT1A mRNA of noise-exposure group was significantly raised(p<0.01), comparing with the normal control group. The AngⅡcontent , the expression of AGT and AT1A mRNA of myocardium of the telmisartan intervention group were decreased significantly(p<0.01), comaring with the noise-exposure group. 6. Noise can cause increased expression of PKC and NADPH oxidase subunits: p47phox, p22phox, gp91phox. Telmisartan was shown to inhibit the expression of PKC and NADPH oxidase subunits.CONCLUSION:1. Heart damaged by noise may be related to oxidative stress injury.2. Noise exposure can stimulate local cardiac RAS.3. Heart damaged by noise may be related to overexpression of PKC and NADPH oxidase.4. Heart damaged by noise may be mediated by Ang II-AT1 pathway.5 Telmisartan can reduce heart injury by blocking the action of Ang II. One of the signal transduction process of noise-induced heart damaged is composed of the following steps: noise exposure induction of overexcitation of cardiac RAS, which increas Ang II levels, binds with AT1A, activates of PKC, increases of P47 expression, and augments NADPH oxidase assembly. Assembled NADPH oxidase has enzyme activity, which then catalyzes electron transport to produce ROS. ROS should be the signal messenger, activating signal pathways, and causing heart injury.