Influence Of Endogenous Carbon Monoxide On Blood Pressure And Cardiovascular Remodeling In Wistar Rats

Hypertension is the most prevelent cardiovascular disease. It is an important hazard to people's health because it can result in target organ damage, such as congestive heart failure, coronary heart disease, stroke, and renal failure. Hypertension is usually accompanied with cardiovascular remodeling ,which is an adaptive and compensatory chang at first. However, the remodeling may cause deleterious consequence. The cardie remodeling is mainly characterized as left ventricular hypertrophy(LVH), which including the increase of left ventricular mass and left ventricular stiffness, the decrease of coronary flow reverse. The degree of increased left ventricular mass is a strong and independent risk factor for cardiac mortality over and above the extent of coronary artery disease. LVH has been regared as an independent risk factor for cardiovascular disease. The vascular remodeling not only has the functional chang which is shown as vessel hypersensitivity to vasocontractor and hyposensitivity to vasodialator, but also has the structural change which includes increase of artery media and cross-sentional area, and relative narrowness of lumen. It will cause decrease of compliance in large arteries and increase of peripheral artery resistance. Vascular remodeling is the result of hypertension , however, it plays an important role in the maintance of hypertension and in the occurrence of target organ damage. It has been proved that benefical outcome will be expected with regression of cardiovascular remodeling. Nowdays, itis realized that only keep on normal blood pressure is not enough for hypertensive patients. Efforts should also be aimed at preventing or regressing cardiovascular remodeling in order to reduce the morbidity and mortality of cardiovascular events. The mechanisms of cardiovascular remodeling are complex. It depends not only on the hemodynamics effect of hypertension but also on the accompanied neural-humoral abnormalities, for example, angiotensin II (Ang II ) and endothelin-1 (ET-1) synthesized in local cardiovascular tissues may play important roles in the occurrence of cardiovascular remodeling. Carbon monoxide(CO) is a kind of gas messenger molecule and neural transmitter. CO is an important factor mediated the function of regulating of vessel tone, blood flow, and blood pressure. CO may directly and indirectly inhibit hypertrophy and hyperplasia of myocardial cells and vascular smooth muscle cells. CO may participate in the pathogenesis of hypertensive cardiovascular remodeling.Objective The animal experiment was designed to investigate the influence of CO on hypertensive cardiovascular remodeling and its possible mechanisms through researching the change of cardiovascular tissues.Methods 32 female Wistar rats were randomly divided into 4 groups(n=8). Group A was normal control group, rats were superalimentated drinking water 2 ml/day for 10 weeks, and intraperitonealy injected sterile distilled water 2 ml/day from 3rd to 10th week. Group B was hyperetensive group, NG-nitro-L-arginate(an inhibitor of nitric oxide oxygenase,L-NNA) solution was superalimentated at the dose of 15 mg-kg-1M-1 for 10 weeks, sterile distilled water was also injected as group A. Group C and D were interventional groups, the using methods of L-NNA were like group B. Hemin chloride(Hm, 15 mg-kg-1-d-1), and Hm(15 mg-kg-1-d-1) + hemin-L-lysinate (HLL 45umol-kg-1-d-1) were injected intraperitonealy from 3rd to 10th week in the two groups, respectively. Systolic blood pressure and heart rate were measured by the tail-cuff method everyday in the first week and thereafter weekly under conscious semi-restrained condition after warming. The dose was adjusted according to body weight which was measured weekly. Rats were anesthetized at 10th week after the last injection of drug. Venous blood samples were collected and cryopreservated for measing the concentrationg of NO in serum, of CO, cyclic guanosine monophosphate (cGMP), Ang II and ET-1 in plasma. The weight of heart and left ventricule (including ventricular septam) were measured after...