大鼠α1肾上腺素受体及其亚型影响β肾上腺素受体介…

在大鼠心脏上同时激动α１肾上腺素受体（α１－ＡＲ）与β－肾上腺素受体（β－ＡＲ），较单独激动β－ＡＲ时产生的ｃＡＭＰ明显减少，α１Ａ－ＡＲ亚型抑制，而α１Ｂ－ＡＲ亚型增强β－ＡＲ刺激ｃＡＭＰ生成的作用。但α１－ＡＲ及其亚型激动不影响ｆｏｒｓｋｏｌｉｎ引起的ｃＡＭＰ生成，亦不影响β－ＡＲ与〔＾１２５Ｉ〕吲哚洛尔的最大结合容量和解离常数。苯福林激动α１－ＡＲ对三磷酸鸟苷使丙肾上腺素与〔＾１２５Ｉ〕ＫＸ     

一种对氯乙基可乐定不敏感对5—methyl—urapidil低亲和的新α1…

用放射配体结合实验方法发现在大鼠心脏中存在一种新的α１肾上腺素受体亚型，这种亚型不同于α１Ａ，α１Ｂ，α１Ｃ及α１Ｄ等以往报道的α１受体亚型，它与α１Ａ一样对ＷＢ４１０１具有高亲和性，但对５－ｍｅｔｈｙｌ－ｕｒａｐｉｄｉｌ呈低亲和，而且对氯乙基可乐定（ＣＥＣ）不敏感。     

可乐定对严重烫伤大鼠心肌Gsα mRNA表达的影响

目的研究可乐定对严重烫伤大鼠心肌Gsα mRNA表达的影响。方法将大鼠置于95℃水浴中烫10 s,造成背部皮肤30%体表面积III度烫伤。分别用dot blotting杂交,原位杂交、放射免疫分析及间接方法测定心肌Gsα mRNA表达水平、cAMP生成量与adenyl cyclase (AC)活性。结果烫伤后3 h心肌Gsα mRNA表达水平明显减少,0.3,1.0,3.0 mg·kg^-1可乐定(ip)可增加烫伤后心肌Gsα mRNA表达,表达相对量与可乐定剂量呈正相关。I₁-咪唑啉受体拮抗剂efaroxan可部分逆转可乐定增加烫伤后心肌Gsα mRNA表达的作用,减少量与efaroxan剂量呈显著正相关。AC和cAMP的变化与Gsα mRNA类似。结论可乐定可增加烫伤后早期大鼠心肌Gsα mRNA表达、AC活性和cAMP产生。     

长期饮用普萘洛尔对大鼠心脏α1肾上腺素受体亚型数…

采用放射配体结合实验，离体左心房收缩功能实验及逆转录聚合酶链反应等方法观察了大鼠长期饮用非选择性β肾上腺素受体拮抗剂普萘洛尔对心脏α１肾上腺素受体亚型分布及其功能的影响。     

可乐定降低眼内压的中枢肾上腺素能机制

目的　探讨可乐定对眼内压 (IOP)的影响以及中枢α 肾上腺素能神经元作用的机制。方法　 3种不同方法给药 :(1)眼球表面滴注可乐定 ;(2 )侧脑室内微量注射育亨宾或哌唑嗪后 ,再分别用可乐定侧脑室内注射和滴眼 ;(3)蓝斑内微量注射可乐定 ,分别观察IOP的变化。结果　可乐定 3种给药方法均有明显降低IOP的效应 ,脑室注射育亨宾能翻转可乐定脑室注射和滴眼降低IOP的效应。结论　通过外周或中枢给可乐定都能降低IOP ,说明中枢α2 受体参与了这一作用     

Effects of clonidine on pituitary-adrenocortical axis in morphine-tolerant rats and after naloxone-induced withdrawal.

The effects of systemically administered clonidine on pituitary-adrenocortical axis in morphine-tolerant rats and after naloxone-induced withdrawal were examined. In naive animals, clonidine (0.5 and 1 mg/kg s.c.) significantly increased plasma beta-endorphin-like immunoreactivity (beta-END-LI) and cortisol levels. This effect was significantly reduced in morphine-tolerant animals. Naloxone treatment induced an increase of plasma beta-END-LI and cortisol levels in morphine-tolerant animals. The increase in cortisol level after withdrawal was significantly reduced by clonidine. These results are consistent with an interaction between alpha 2-adrenoceptors and opioid systems in the control of pituitary-adrenocortical axis during morphine tolerance and withdrawal.     

Dosage of beta-adrenergic blockers after myocardial infarction.

Dosages of beta-adrenergic blockers prescribed after myocardial infarction (MI) in a Veterans Affairs medical center were reviewed to determine if dosages were adjusted to target dosages used in clinical trials. The medical records of all patients with a discharge diagnosis of MI were reviewed. The target dosage, selected from major clinical trials, was atenolol 100 mg/day p.o., metoprolol tartrate 200 mg/day p.o., or propranolol 180-240 mg/day p.o. A systolic blood pressure of < or = 100 mm Hg and pulse rate of < or = 50 beats/min were defined as the clinical markers of the maximum tolerated beta-blocker dosage. A discharge diagnosis of MI was identified in 396 patients between January 1999 and December 2000, and 106 patients met the inclusion criteria. The patients had a mean +/- S.D. age of 66.3 +/- 10.7 years, 98% were men, and all received either atenolol or metoprolol. The mean +/- S.D. systolic and diastolic blood pressure and pulse rate on admission were 135 +/- 30 and 75 +/- 18 mm Hg and 80 +/- 20 beats/min, respectively. The mean +/- S.D. dosages for atenolol and metoprolol were 54 +/- 39 and 90 +/- 77 mg/day at the time of discharge, 54 +/- 38 and 95 +/- 81 mg/day at 6 months after discharge, and 53 +/- 40 and 82 +/- 80 mg/day at 12 months, respectively. Only 15% of the patients reached the target dosage, as defined in clinical trials, of a beta-blocker. No reason for maintaining the beta-blocker dosage was documented for 65% of the patients. Beta-blockers were prescribed frequently after MI but usually were not used at dosages that matched those in clinical trials.     

Effects of moxonidine and clonidine on potassium excretion in Sprague-Dawley rats.

Recently we demonstrated that clonidine and moxonidine exert specific action on fractional fluid and Na+ excretion in anaesthetised Sprague-Dawley rats. Classically, most of the diuretics used induce an increased K+ excretion, at least in part due to Na+ load in the distal tubule and exchange of Na+ by K+. Therefore, we studied the effects of moxonidine and clonidine on K+ excretion in anaesthetised Sprague-Dawley rats. Moxonidine (0.25 and 0.5 mg kg-1 body wt. i.v.) increased transiently K+ (1.0 +/- 0.3 -1.9 +/- 0.4 and 0.9 +/- 0.2 -2.9 +0.7 micromol min-1 100 g body wt.) and Na+ (1.4 +/- 1.0 -6. 9 +/- 3.1 and 0.8 +/- 0.36 -6.6 +/- 1.5 micromol min-1100 g body wt.) excretion. Clonidine (0.25 mg kg-1) caused a more pronounced increase in K+ (1.0 +/- 0.1 -2.7 +/- 0.4 micromol min-1 100 g body wt.) and Na+ (0.6 +/- 0.3 -9.5 +/- 0.4 micromol min-1 100 g body wt.) excretion, whereas the higher dose of 0.5 mg kg-1 body wt. had less effect as compared to moxonidine (K+: 0.8 +/- 0.1 -1.7 +/- 0.2 micromol min-1 100 g body wt., Na+: 0.3 +/- 0.1 -3.4 +/- 1.0 micromol min-1 100 g body wt.). The increased electrolyte excretion returned (similar to moxonidine) to baseline levels within 20 min after injection of the drugs. Antagonists such as idazoxan and yohimbine did not change K+ and Na+ excretion by their own. Both, the non-selective imidazoline/alpha2-adrenoceptor antagonist idazoxan and the pure alpha2-adrenoceptor antagonist yohimbine attenuated the moxonidin-induced effects on K+ and Na+ excretion. This could be also observed with clonidine and simultaneous injection of these two antagonists. Our results demonstrate that moxonidine and clonidine also increase renal K+ excretion in this animal model. K+and Na+ excretion show a parallel behaviour, indicating that the increased K+ excretion is mainly due to Na+ load in the tubular system.     

Effects of clonidine on experimental stomach ulcer in rats

Clonidine 2 mg/kg ig inhibited the rat gastric ulcers induced by pyloric ligation, stress and indomethacin by 71%, 77% and 82%, respectively. Clonidine 2 mg/kg ig tended to accelerate the healing of gastric ulcer induced by acetic acid, and the healing rate was 61%. Clonidine decreased the secretion of gastric acid and pepsin, and increased the release of gastric barrier mucus. These actions may contribute to its protective effect against ulceration.     

Chronic effects of metoprolol on myocardial beta-adrenergic receptors in doxorubicin-induced cardiac damage in rats.

This study was designed to clarify whether chronic administration of metoprolol had any influence on cardiac beta-adrenergic receptors (BAR) in doxorubicin (DOX)-induced cardiac damage. DOX was injected through the tail vein into rats (3 mg/kg/week, n = 22) for 5 weeks. One week after the final injection, the rats were randomly divided into two groups, M (with metoprolol, 10 mg/kg/day subcutaneously, s.c.; n = 11) and D (without metoprolol; n = 11). After 3-week infusion, plasma norepinephrine (NE) levels and BAR density [[125I]iodocyanopindolol (ICYP) binding on crude membranes] were measured. Left and right ventricular end-diastolic pressure (LVEDP, RVEDP) and myocardial NE levels were also measured, and the results were compared with those from an age-matched control group (C n = 11). Decreased BAR density and increased plasma NE levels were evident in group D, indicating downregulation. In group M, BAR density and plasma NE levels were similar to those in group C. The myocardial NE levels were decreased in group D, but were higher in group M than in group D. The LVEDP and RVEDP were increased in group D, but were almost normal in group M. These results suggest that metoprolol is a promising drug for treatment of DOX-induced cardiac damage.     

曲美他嗪对心肌梗死后心力衰竭大鼠心肌自噬水平的影响

摘要： 目的 观察心肌梗死 （MI） 后心力衰竭 （心衰） 大鼠应用曲美他嗪后左心功能及心肌自噬水平的变化。方法 健康雄性 Wistar 大鼠 20 只结扎左冠状动脉前降支近段, 4 周后随机分为模型组 （M 组）、 曲美他嗪组 （Q 组）, 每组 10 只, 另设假手术组 （S 组） 10 只, Q 组给予曲美他嗪 15 mg·kg-1 ·d-1 , 用药 4 周后, 使用小动物超声仪检测左室心功能水平, PV-Loop 压力-容积系统测量大鼠血流动力学水平, 酶联免疫吸附试验测定 （ELISA） 法检测大鼠血清 N- 末端脑钠肽前体 （NT-proBNP） 和超敏肌钙蛋白 T （hs-TnT） 水平, HE 和 Masson 染色观察心肌病理学改变和纤维化情况, TUNEL 荧光染色检测心肌细胞凋亡情况, Western blot 法和 RT-PCR 检测心肌组织自噬相关蛋白和基因的表达水平。结果 （1） 曲美他嗪显著改善了大鼠 MI 后心衰引起的左室扩张和功能障碍。（2） 曲美他嗪显著改善了心衰引起的压力负荷加重、 左室顺应性降低。（3） 曲美他嗪减轻了心衰大鼠心肌细胞水肿、 坏死以及心肌纤维化。（4） ELISA 结果显示, 曲美他嗪显著改善了大鼠心衰引起的血清 NT-proBNP 和 hs-TnT 水平升高。（5） 曲美他嗪降低了心衰引起的心肌细胞凋亡。（6） Western blot 和 RT-PCR 结果显示, 曲美他嗪可上调心衰大鼠心肌自噬水平, 并且增加心肌自噬流的活化。结论 自噬对心肌细胞有保护作用, 曲美他嗪可通过上调 MI 后心衰大鼠心肌细胞自噬水平, 改善心功能。     

Effects of clonidine on the experimental hypertension by abdominal aortic coarctation in rats.

Cardiovascular baroreflex mechanisms and sympathetic tone could be involved in the arterial hypertension by coarctation of abdominal aorta artery (CoA). The present work analyzes the effect on the arterial pressure and heart rate (HR) of the clonidine, an alpha(2)-adrenergic central acting antihypertensive agent, after intravenous (i.v.), intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration in rats anesthetized with pentobarbital (40 mg/kg i.p.).Wistar rats of both sexes (240-270 g) were used to the 7 days of the CoA or a sham operation (SO). Values of mean arterial pressure (MAP) and of HR were calculated from intraarterial recordings of blood pressure.The MAP of the CoA rats (161.5+/-5.3 mmHg, n=20) was significantly higher (P<0.01) than that of the SO rats (101.6+/-3.3 mmHg, n=20).The i.v. injection of clonidine (3-30 microg/kg) produced an increase of blood pressure in the rats SO and in the CoA animals, followed by a fall of arterial pressure in both groups of rats. Clonidine showed a small pressor effect but also a great depressor action in the hypertensive rats. Except for with the dose of 10 microg/kg, differences in cardiac response to clonidine were not seen in both groups of rats.Injection of clonidine by the i.c.v. via (10 microg) like by the i.t. (3 microg) also produced a greater fallen of the MAP in the hypertensive rats than in the controls SO animals.In conclusion, these hypertensive animals would be sensitive to the antihypertensive action of central acting alpha(2)-adrenoceptor agonist clonidine administered by different ways, suggesting a great sensitivity of the post-synaptic alpha(2)-adrenoceptor of central nervous system.     

Pulmonary ventilation in long-term beta-adrenergic blockade after myocardial infarction

In a double-blind, randomized study, the long-term effects of timolol and placebo on FEV1, PEFR, FVC, VC, respiratory rate and heart rate were compared in 32 patients surviving acute myocardial infarction, 17 on timolol and 15 on placebo. The patients were assessed before and after 1, 3 and 6 months of medication, and then every 6 months for up to 2 years; the mean observation period was 17.4 months. Timolol decreased FEV1 significantly (9-17%) throughout the study. PEFR and FVC fell by 4-13% and 9-11%, respectively, on timolol; the reductions were significant at 3, 6 and 24 months, and at 1, 3 and 6 months, respectively. VC showed only small changes and respiratory rate did not change. In only one patient were the changes in pulmonary function of clinical relevance. Thus, significant, persisting airways dysfunction was induced by long-term beta-adrenergic blockade in patients surviving myocardial infarction.     

吡维氯铵对心肌梗死大鼠心肌纤维化和心脏功能的影响

目的探究吡维氯铵对急性心肌梗死大鼠心肌纤维化和心脏功能的影响。方法分离并体外培养大鼠心肌成纤维细胞,设置正常环境和缺血缺氧环境,采用不用质量浓度(1,2,4,8,16,32和64μg·L~(-1))的吡维氯铵作用于大鼠心肌成纤维细胞48 h,采用台盼蓝染色和血细胞计数板计数评价细胞存活率。结扎冠状动脉左前降支建立大鼠急性心肌梗死模型,将大鼠随机分为假手术组、心肌梗死组和吡维氯铵治疗组。急性心肌梗死术后14 d处死大鼠,采用心肌组织Masson染色评价心肌纤维化程度;采用α平滑肌肌动蛋白(α-SMA)染色观察心肌成纤维细胞的形成;测定羟脯氨酸含量评价心肌胶原含量;采用CD31染色评价毛细血管密度;采用超声心动图评价心脏功能。结果在缺血缺氧环境中,吡维氯铵能明显抑制心肌成纤维细胞的增殖,其IC_(50)值为11.7μg·L~(-1);而吡维氯铵对正常条件下心肌成纤维细胞无抑制作用。与假手术组比较,心肌梗死组出现心肌梗死和心肌纤维化。与心肌梗死组大鼠比较,吡维氯铵治疗组心肌纤维化程度明显降低(P<0.01);α-SMA和心肌成纤维细胞数量明显减少(P<0.01);心肌胶原含量明显下降(P<0.05);CD31和毛细血管密度明显增加(P<0.01);治疗后大鼠左心室射血分数和左心室缩短分数明显改善(P<0.01),左心室舒张期末和收缩期末内径减小(P<0.05)。结论吡维氯铵能抑制急性心肌梗死后大鼠心肌纤维化,增加毛细血管新生,改善心功能。