Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats.

Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.     

Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats

Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal.     

Cold-induced changes in blood lipoproteins in normotensive and hypertensive rats

It is shown that in thermoneutral conditions ISIAH (Inherited Stress-Induced Arterial Hypertension) hypertensive rats had a lower level of high-density lipoproteins (HDLP) in plasma and a higher atherogenic coefficient compared to normotensive Wistar rats. After cooling there were different changes in fractional composition of plasma lipoproteins both in normo- and hypertensive rats. These changes depended on the cooling rate and were more pronounced after slow cooling. Slow cooling resulted in a more significant increase of plasma HDLP and in a greater decrease in LDLP and atherogenic coefficient in hypertensive rats compared to normotensive ones.     

The early ontogeny of sodium appetite in spontaneously hypertensive vs. normotensive rats

Rats of various strains differ widely in their appetite for sodium. For example, the Okamoto-Aoki spontaneously hypertensive rat (SHR) exhibits a much greater salt appetite than its normotensive control strains. Developmental observations of salt appetite in this strain have been collected only for rats at or above weanling age. In this experiment, the salt appetite of the SHR was compared with that of normotensive Sprague-Dawley and Wistar-Kyoto rats, at 3, 6 and 12 days after birth. The results show that the increased salt appetite of the SHR is a fundamental behavioral trait that appears very early in life. This observation is consistent with a defective central angiotensin system in SHR rats.     

Cardiovascular changes during the sleep-wake cycle in spontaneous hypertensive rats and in their genetically normotensive precursors

Blood pressure and heart rate were recorded in spontaneously hypertensive rats (SH) and in their genetically normotensive precursors (WKY) during the sleep-wake cycle using a computer-assisted method. Similar results were obtained in both strains: (a) No significant difference was observed in blood pressure values between slow-wavesleep (SWS) and the last 2 min of the preceding wakefulness (W) episode within the complete cycle; blood pressure then increased duringPS. (b) Heart rate values during SWS were significantly lower than those computed for W; a further fall of heart rate was observed during paradoxical sleep (PS) only in hypertensive rats. (c) During SWS the blood pressure and heart rate variability was significantly lower than during W and PS. In addition, blood pressure variability values during the three sleep-wake states were lower in hypertensive than in normotensive rats. These data suggest that there are no qualitative differences in the mechanisms that control eirculation during sleep in normotensive and spontaneous hypertensive rats.     

Circadian changes in heart rate in unanesthetized normotensive and spontaneously hypertensive rats

Circadian changes in heart rate and heart rate variability were measured in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Electrocardiograms (ECG) were continously recorded, over a 24 hour period from freely moving conscious rats via three small metallic subcutaneous electrodes which were positioned a week before the recording period. The findings reported here show:

1. Mean heart rate calculated over 24 hours were lower in both strains than previously reported. This difference probably reflects the lack of anesthesia and minimal stress in the present study.
2. The timing of the circadian variations in both strains were the same, suggesting that were both entrained to the light-dark cycle.
3. The 24 hours mean heart rate variability was significantly higher in SHR than in WKY but in each strain it was similar throughout the 24 hours. This suggests that the vagal tone in SHR was higher by a fairly constant amount throughout the light-dark cycle.

     

Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats.

Antioxidant enzyme activities and oxidative stress were evaluated in the myocardium in relation to hemodynamic function subsequent to myocardial infarction in rats. One week after the coronary ligation, the left ventricular peak systolic pressure, left ventricular end-diastolic pressure, and aortic pressures remained near control values and there were no differences in lung and liver wet/dry weight ratios between experimental and control animals. In the 4-, 8-, and 16-week experimental animals, there was a progressive drop in left ventricular peak systolic pressure and an increase in left ventricular end-diastolic pressure. Aortic systolic pressure was depressed at 8 and 16 weeks. In myocardial infarct rats, there was a significant increase in wet/dry weight ratio of lungs at 8 weeks and at 16 weeks; this ratio was increased for lungs as well as liver. Based on the hemodynamic data as well as other observations, animals in the 1-, 4-, 8-, and 16-week groups were arbitrarily categorized into nonfailure and mild, moderate, and severe failure stages, respectively. In the nonfailure stage, there was a marginal increase in superoxide dismutase, glutathione peroxidase, and catalase activities as well as vitamin E levels. The redox state in these hearts, assessed by the reduced/oxidized glutathione ratio, was significantly increased. Superoxide dismutase activity was unchanged in mild and moderate failure stages but significantly depressed at 16 weeks. Glutathione peroxidase and catalase activities showed progressive decreases through mild, moderate, and severe failure stages. Vitamin E levels were significantly depressed at moderate and severe failure stages. There was a progressive increase in lipid peroxidation at mild, moderate, and severe stages of heart failure and the redox ratio was significantly depressed in the severe failure stage. These data suggest that heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress.     

Changes in gluco- and mineralocorticoid adrenal functions in spontaneously hypertensive rats during experimental myocardial infarction

The dynamics of corticosterone and aldosterone contents during the acute and restoration periods of experimental myocardial infarction was studied in Wistar and spontaneously hypertensive rats. In spontaneously hypertensive rats, the increase in aldosterone concentration during the acute period was followed by elevation of corticosterone content, which attested the disadaptive course of experimental myocardial infarction against the background of hereditary arterial hypertension. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 1, pp. 25–27, January, 2000     

Hormonal changes during experimental hypothalamic obesity in rats

Conclusions The following changes were observed in rats with experimental hypothalamic obesity: an enhancement in the function of the pancreatic insular apparatus; an increase in hypophyseal STH biosynthesis and secretion; a decrease in hypophyseal thyrotropic function and thyroid gland activity, with disturbances in thyroid hormone metabolism in target tissues; lack of changes or a decrease in adrenal glucocorticoid function; an enhancement of lipogenesis; a decrease in the content of cAMP in a number of organs and tissues.Translated from Problemy éndokrinologii, Vol. 24, No. 1, pp. 55–60, January–February, 1978.     

Regional blood flow in normotensive and spontaneously hypertensive rats.

Regional distribution of cardiac output in unanesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar NR male rats (10 each group; average age 21 wk) was determined using two 15-mum microspheres (141Ce and 85Sr) injected 10 min apart through a left ventricular (LV) cannula. Fractional flow distribution was expressed as percentage activity of injected dose (average of the two measurements). Despite differences in body and organ weights, organ flow distribution did not vary between SHR and WKY, except for heart and testes (P less than 0.025). However, differences did not exist between SHR and NR with respect to heart, brain, lungs, spleen, and adrenal flows (P less than 0.05).     

急性心肌梗塞的血液流变学变化

本文观察了AMI家兔术前及术后24h的血液流变学变化。发现AMI组的校正粘度、红细胞和血小板电泳时间均明显高于对照组。血浆粘度变化两组相似。表明AMI时的血液流变学变化部分与应激反应有关,也可能还受其它一些因素的影响。     

Stress ulcer in normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and their normotensive progenitors, the Wistar-Kyoto (WKY) rats, were tested in the open-field arena and subsequently exposed to either cold-restraint stress or activity-stress. SHR rats were more active and judged less fearful in the open-field test. Changes in core body temperature, and adrenal and thymus weights did not differentiate between SHR and WKY rats in the cold-restraint procedure. A significant adrenal hypertrophy was observed for SHR rats in the activity-stress procedure. WKY rats were more susceptible to stress ulcer in both the cold-restraint and the activity-stress procedures. While running-wheel activity had been considered an important etiological variable for activity-stress ulcer, the lower activity demonstrated by the ulcer-prone WKY rats suggested that genetic variables might be more relevant to stress ulcer disease.     

Potassium and myoglobin release and ST and QRS vector changes during acute myocardial infarction

Thirty-three consecutive patients aged 39 to 77 years with signs of myocardial infarction with a duration of symptoms of less than 4 h took part in the study. Serial blood sampling was done for the determination of myoglobin (MG), creatine-kinase (CK) and potassium (K). Continuous vectorcardiography was monitored. Peak rates of K and MG release occurred 7.0 +/- 3.7 and 6.5 +/- 3.9 hours, respectively, after the onset of symptoms not different from the end of ST vector change that occurred after 7.6 +/- 2.8 h. Following the end of ST vector change there was a 4-hour delay until the end of QRS vector change and another 8-hour delay to the end of MG release occurring about 20 h after the onset of symptoms. At the time for peak rate of MG release 48 +/- 17% of total MG release had occurred. In conclusion, the physiologically different indicators of myocardial damage showed signs of maximum release within the same time range, 6-8 h after the onset symptoms and 8-10 h before signs of completed infarction.     

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

促红细胞生成素抑制急性梗死心肌炎症因子的表达

背景：研究表明,炎症细胞因子可影响心肌梗死后的预后,在心脏重构的进程中起重要作用。同时促红细胞生成素的促红细胞生成之外的非造血效应也被广泛证实：促红细胞生成素可通过与靶细胞膜表面的促红细胞生成素受体结合而减少炎症反应,从而减少心肌缺血后的再灌注损伤。 目的：观察重组人促红细胞生成素对大鼠急性心肌梗死后心脏重构中炎症因子表达的影响。 方法：通过结扎左冠状动脉前降支建立SD大鼠急性心肌梗死模型,分为5组,假手术组注射生理盐水,手术对照组造模后注射生理盐水,SB203580组造模后注射p38 MAPK的高选择性阻断剂SB203580,促红细胞生成素组造模后注射促红细胞生成素注射液,促红细胞生成素+SB203580组造模后注射促红细胞生成素+ SB203580混合液,分别在造模前、造模后1 d、1周、2周及4周进行尾静脉采血,酶联免疫吸附法检测血清中白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平变化。 结果与结论：造模前各组大鼠血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α检测值差异均无显著性意义(P > 0.05)。假手术组各时段白细胞介素1β、白细胞介素6、肿瘤坏死因子α检测值差异无显著性意义(P > 0.05),其余4组不同时段各因子检测值呈现造模后1 d最高,造模后4周回降的趋势(P < 0.05)。造模后手术对照组血清各因子检测值较其他组升高明显,而假手术组血清各因子检测值均低于其他4组(P < 0.05);使用药物进行干预的3组中,促红细胞生成素+SB203580组各因子检测值较低(P < 0.05),而促红细胞生成素组与SB203580组各因子检测值差异无显著性意义(P > 0.05)。提示重组人促红细胞生成素抑制了大鼠急性心肌梗死后心脏重构中炎症因子白细胞介素1β、白细胞介素6、肿瘤坏死因子α的表达,重组人促红细胞生成素抑制炎症因子表达的机制可能与转化生长因子β1-TAK1-p38 MAPK信号路径相关。     

自身免疫反应参与大鼠急性心肌梗死后心肌损伤的实验研究

目的：探讨急性心肌梗死(AMI)后自身免疫在心肌损伤和心室重塑中的作用。方法： 在体结扎Wistar大鼠冠状动脉左前降支(LAD)，建立AMI大鼠模型和假手术对照。6周后将其脾细胞(100×106-150×106)过继转输给同源近交大鼠；4周后血流动力学监测心功能改变，ELISA检测大鼠血清抗肌球蛋白重链(MHC)抗体，组织学检查心肌病理改变，免疫组化分析浸润心肌T细胞表型。 结果：AMI大鼠(n=12)心肌非梗死区可见异常炎症反应，所有过继转输大鼠(AMI-T)(n=10)发生器官特异性心肌炎症反应，免疫组化染色显示心肌出现CD4+T细胞浸润，假性手术转输组(sham-T)(n=10)均为阴性；AMI大鼠和AMI-T大鼠血清中检出抗MHC抗体(8/22)，sham-T组均为阴性(阳性率36.4% vs 0.0%)，(P＜0.05)；与sham-T组比较，AMI-T组发生左心室收缩功能受损(+dp/dtmax:1 323±55 kPa/s vs 1 418±82 kPa/s,P＜0.05)。 结论：自身免疫反应参与AMI后心肌损伤，可能是AMI后心室重塑的新机制。