| Background and objective Hypertension is the most important risk factor for cardiovascular disease. Therefore, the study on the pathogenesis and control of hypertension has become a worldwide hot topic. The pathogenesis mechanism of hypertension is very complex. At present , it is generally believed that environmental factors may be one of the reasons . AngiotensinⅡ(AngⅡ), the circulation and local rennin - angiotensin system important molecular, has become play an important role in myocardium and vascular tissue pathological remodeling the process. It is not only on the development and maintenance of the mechanism plays an important role in hypertension, but also directly induced the proliferation of cell, and extracellular matrix synthesis increased, besides , other growth factors and synthesis of biologically active substances released. A growing body of studies has shown that AngⅡis activation of NADPH oxidase the most important stimulating factor,Vessel wall at the floors are all NADPH oxidase subunit distribution, and there is a corresponding dynamic changes. AngⅡinduced reactive oxygen species (ROS) and oxidative stress is closely related to cardiovascular disease and the development process, a variety of animal models of hypertension have been observed increased levels of ROS , neurohumoral factors caused by a variety of pathological changes in relation to increased the induction of ROS . ROS not only directly lead to tissue and cell injury, and ROS themselves are important signaling molecules, can activate a variety of oxygen-sensitive kinases and transcription factors, thereby regulating gene expression in a variety of proteins. Heat stress has a wide range of organisms, the body can cause hypertension and its many organizations, multiple organ injury, heat stress can promote ROS generation in the body, involved in regulation of the process of stress injury. Nevertheless the expression of ROS in the mechanism of heat stress is not yet clear. Angiotensin-converting enzyme inhibitor (captopril) is widely used in clinical treatment of hypertension , it is apply to a variety of animal models of hypertension. It is wellknown that antioxidants (vitamin C) is a very important free radical scavenger, not only effectively clear the 02-,H202,0H and 02 many other reactive oxygen species, but also a large number of animal experiments have confirmed its anti-oxidation. Angiotensin converting enzyme inhibitors and antioxidants in heat stress conditions with the heart protective effect is not yet clear. This study was therefore designed to observe chronic high-temperature stimulation on the rat effect of blood pressure and cardiac morphology; to study heat stress on myocardial effects of AngⅡ, and its relationship with ROS and p22phox ; to investing the effects and mechanism of angiotensin-converting enzyme inhibitors and antioxidants in the prevention and protection heat stress-induced cardiac damage . The purpose of the study is to elucidate cardiac molecular mechanisms of cardiac damage associated with heat stress and the interventional effects of drugs on it, and provide novel theoretical evidences and strategy for prevention and treatment of heat stress-induced cardiac damage.Methods In this study, heat stress rats were used as experiment models. Carotid artery cannulation, radioimmunoassay, colorimetric method, reverse transcription polymerase chain reaction ( RT-PCR ), immunohistochemistry and other methods and techniques were applied to identify:(1) the changes of plasma and myocardial of AngⅡin heat stress rats;(2) the changes of ROS levels of and expression of p22phox in heat stress rats myocardial and its relationship with AngⅡ;(3) the effect of angiotensin converting enzyme inhibitors and antioxidants on the AngⅡ,ROS levels and expression of p22phox in heat stress rats.Results (1) Four weeks after heat stress ,compared with the control group , MBP in the heat stress group and the high temperature and high humidity stress group were increased and the deviation were highly significant(133.68±5.30mmHg,129.49±6.36mmHg vs 100.45±7.38 mmHg,P<0.01.); (2) LVW/BW index had no significant deviation between each group(2.10±0.14,2.15±0.16 vs 2.05±0.16, P >0.05);(3) Compared with control group, the concentration of AngⅡin the plasma and the myocardium increased markedly(140.06±63.55ng/L,348.15±43.00ng/L vs 325.56±38.92ng/L, P<0.01; 710.47±55.82ng/L,993.67±171.42 ng/L vs 1011.68±115.26 ng/L,P <0.01);(4) Compared with control group , ROS levels of myocardium was increased significantly (SOD 255.52±25.25 U/mgprot,177.08±32.65 U/mgprot vs 186.13±29.80 U/mgprot, P<0.01;MDA 6.01±1.84 nmol/mgprot,10.13±32.65 nmol/mgprot vs 11.15±3.10 nmol/mgprot ,P <0.01.);(5)Compared with control group ,expression of p22phox mRNA levels of myocardium were increased markedly(0.45±0.07,0.46±0.07 vs 0.22±0.05,P <0.01);(6)Compared with control group , p22phox protein levels of myocardium were increased significantly(0.25±0.03,0.24±0.02 vs 0.17±0.02,P <0.01);(7) Four weeks after high temperature and humidity stress, compared with the control group , temperature and humidity group was increased (100.45±7.38 mmHg vs 129.49±6.36 mmHg,P<0.01), compared with temperature and humidity group, Captopril group and vitC group were decreased (107.78±13.75 mmHg, 111.35±8.25 mmHg vs 129.49±6.36 mmHg ,P<0.01);(8) LVW/BW index had no significant deviation between each group(2.15±0.14,2.05±0.19 ,2.08±0.16 vs 2.13±0.17, P >0.05);(9) Compared with control group, the concentration of AngⅡin the plasma and the myocardium increased markedly(325.56±38.92ng/L vs 140.06±63.55ng/L, P<0.01,1011.68±115.26ng/Lvs 710.47±55.82 ng/L, P<0.01); compared with temperature and humidity group, Captopril group and vitC group were decreased markedly(113.94±64.91ng/L,89.64±26.94ng/L vs 325.56±38.92ng/L ,P<0.01, 762.75±82.54 ng/L ,770.83±120.87 ng/L vs 1011.68±115.26 ng/L,P<0.01);(10) Compared with control group , ROS levels of myocardium was increased significantly(SOD:186.13±29.80 U/mgprot vs 255.52±25.25 U/mgprot, P<0.01, MDA:11.15±3.10 nmol/mgprot vs 6.00±1.84 nmol/mgprot, P<0.01) , compared with temperature and humidity group, Captopril group and vit C group were decreased markedly( SOD:236.36±31.85 U/mgprot ,239.25±38.71 U/mgprot vs 186.13±29.80U/mgpro,P<0.01,5.31±2.69 nmol/mgprot , MDA:3.37±2.70 nmol/mgprot vs 11.15±3.10 nmol/mgprot, P <0.01); (11) Compared with control group , p22phox mRNA levels of myocardium were increased significantly(0.45±0.07 vs 0.22±0.06,P <0.01),compared with temperature and humidity group, Captopril group and vitC group were decreased significantly(0.20±0.05,0.24±0.06 vs 0.45±0.07,P <0.01);(12) Compared with control group, p22phox protein levels of myocardium were increased significantly(0.24±0.02 vs 0.17±0.02,P<0.01),compared with temperature and humidity group, Captopril group and vitC group were decreased markedly(0.20±0.02,0.19±0.02 vs 0.24±0.02,P<0.01).Conclusion Heat stress can up-regulate blood pressure in rats. Although heart morphology has no increased significantly, probably with the experimental exposure time is correlation with short or small sample size. The concentration of AngⅡin the plasma and the myocardium is increased in heat stress conditions, AngⅡ-mediated increased myocardial tissue ROS levels generation, Its mechanism may be related to heat stress induced expression of p22phox long, This means that the heat stress can cause myocardial damage. Angiotensin converting enzyme inhibitors and antioxidants can inhibit the rat blood pressure, expression of AngⅡis decreased, down-regulate p22phox mRNA and protein expression level of myocardial tissue ,at the same time , ROS levels are reduced, This means that the angiotensin converting enzyme inhibitors and antioxidants on the heat stress-induced cardiac damage play a protective role. In short,heat stress can up-regulate blood pressure in rats, the latter is the plasma and myocardial AngⅡincreased . AngⅡcan up-regulate expression of mRNA and protein levels ,heat stress involved in the oxidative stress injury in the occurrence and development, and further confirmed that AngⅡcan induce ROS generation . Angiotensin converting enzyme inhibitors and antioxidants inhibited AngⅡ, ROS and expression of p22phox. ROS is involved in mechanism of heat stress cardiac damage. Angiotensin converting enzyme inhibitors and antioxidants on the heat stress-induced cardiac damage play a protective role. These will provide novel strategy and theoretic evidence to prevention and treatment of heat stress-induced cardiac damage. |
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