Under Cold Stress Effect Of Different Drugs On The Level Of Systolic Blood Pressure And Left Ventricular Hypertrophy In Spontaneously Hypertensive Rats

Objective:To observe Under cold stress effect of different drugs on systolic blood pressure (SBP), left ventricular hypertrophy(LVH),nitric oxide(NO), angiotensinⅡ(AngⅡ) And the level of endothelin-1(ET-1) in spontaneously hypertensive rats(SHR).Methods:Forty 10-week-old SHRs with 200g were randomly divided into five groups (n =8), namely, SHR control group (SHR-C),cold stress SHR control group (C-SHR-C), cold stress SHR metoprolol group (C-SHR-M), cold stress SHR amlodipine treatment group (C-SHR-A), cold stress SHR benazepril treatment group (C-SHR-B, During the experiment weight and systolic blood pressure and heart rate of each rat was examined once, systolic blood pressure (1 mmHg=0.133kPa) was examined by tail artery pressure measurement methods. Every morning around 8 am, according to the body weight (BW), SHR control group(SHR-C) and cold stress SHR control group(C-SHR-C):1 mL/100 g were given by intragastric administration with 0.9% Nacl. Cold stress SHR metoprolol group (C-SHR-M, metoprolol 50mg/kg·d), cold stress SHR amlodipine treatment group (C-SHR-A, amlodipine 2.5mg/kg·d), cold stress SHR benazepril treatment group (C-SH-B benazepril 10mg/kg·d). After each treatment C-SHR-C, C-SHR-M, C-SHR-A and C-SH-B were placed refrigerator of (4±1)℃for 6h.. Cold stress and medication were on at the same time.. After 6 weeks all SHRs were killed by bleeding, weighing SHR left ventricle weight (LVW). The levels of ET-1 and AngⅡwere measured by radioimmunoassay in plasma and cardiac muscle and the levelof NO were measured by the chemical assay in plasma and cardiac muscle. A portion of the heart specimens were examined by HE and MASSON staining.. endothelinA receptor mRNA.was examined by RT-PCR.Results:The results of the experimental data show:cold stress led to increased SBP of SHR. In the first week SBP is significantly increased and in the first 3 weeks SBP reach to peak (24 mmHg), then SBP was on a high platform. After treatment SBP of all treatment groups were reduced to some extent and at the end of the sixth week SBP in each treatment group were lower than the SHR which did not receive cold stress.SBP, that treatment can not only prevent blood pressure to increase in cold stress, but also make SBP lower than increased range in C-SHR-C Under cold stress. Comparison of blood pressure among the groups suggest:after 3 weeks SBP of C-SHR-A was decreased to the most obvious level, followed for the C-SHR-M, then for the C-SHR-B. Compared with SHR-C, left ventricular mass index of C-SHR-C was significantly higher. Compared with C-SHR-C, left ventricular mass index of C-SHR was significantly lower, in accord with the decrease of blood pressure, LVMI of C-SHR-M and the C-SHR-B were low too, but they are no statistical difference.. Cold stress led to reduction in the level of plasma NO. Compared with C-SHR-C, the level of plasma NO in three treatment groups were increased, especially in C-SHR-A The level of plasma AngⅡin all groups were No significant changes The level of plasma ET-1 in all groups were No significant changes either. Cold stress led to significant increase the level of myocardial ET-1. Although t Cold stress led to he reduction in the level of myocardial NO, they were no statistical difference. Compared with C-SHR-C, the level of myocardial AngⅡin all groups were No significant changes. PCR electrophoresis of Cardiac ETA receptors mRNA and absorbance ratios of myocardial ETA receptors and GAPDH in each group show:In cold stress C-SHR-C mRNA expression in cardiac ETA receptors was significantly higher than SHR-C (P<0.01,), and Compared with C-SHR-C, in C-SHR-A ETA receptor mRNA expression was significantly decreased (P<0.01),but ETA receptor mRNA expression were No significant changes in C-SHR-M and the C-SHR-B (P> 0.05).Myocardium (left ventricular posterior wall) pathology measurement (HE stain) shows:Compared with SHR-C, in C-SHR-C part of the cardiac myofilaments was arranged in disorder, fracture,and myocardial hypertrophy, the enlarged nuclei and deeper cytoplasm were oberserved. Compared with C-SHR-C they were relatively improved in all treatment groups, especially in C-SHR-A most obviously. Myocardium (left ventricular posterior wall) pathology testing (MASSON staining) shows:In SHR-C muscle gap were wide, and occupied in a small amount of collagen. Compared with SHR-C, in C-SHR-C muscle gap were obviously wider, and collagen of muscle interstitial were increased significantly too, Compared with C-SHR-C they were relatively improved in all treatment groups, especially in C-SHR-A most obviously.The result was consistent with the statistics.Conclusion:1. cold stress lead to increased SBP of SHR significantly.2 long-acting calcium channel blocker amlodipine reduce the SBP and LVMI of SHR in cold stress thanβreceptor blocker metoprolol and angiotensin-converting enzyme inhibitor benazepril.3 The mechanism of reduced SBP of SHR with drugs in cold stress may be related to the increased level of plasma NO.the mechanism of inhibition of LVMI may be associated with decreased level of myocardial ET-1 content, and downregulation of myocardial ETAR...