山麦冬总电甙对实验性心肌缺血的影响

用两个模型研究山麦冬总皂甙（ＴＳＬＳＬ）对实验性心肌缺血的影响，结果显示，ＴＳＬＳＬ（４０ｍｇ·ｋｇ－１，ｉｐ）可明显降低Ｉｓｏ所致大鼠心肌缺血模型血清ＣＰＫ水平和心电图ΣＳＴ段变化．在结扎冠脉所致心肌梗塞实验中，ＴＳＬＳＬ（６０ｍｇ·ｋｇ－１，ｉｐ）可显著抑制心肌组织ＣＰＫ的释放，同时ＴＳＬＳＬ能保护心肌ＳＯＤ活性，降低心肌ＭＤＡ水平，此外还降低心肌ＦＦＡ的生成，缩小心肌梗塞面积．实验结果表明，ＴＳＬＳＬ对实验性心肌缺血有保护作用，其作用机制可能与防止心肌细胞脂质过氧化及改善脂肪酸代谢有关。     

Isoproterenol-induced hypertrophy may result in distinct left ventricular changes

1. The aim of the present study was to analyse the possible lack of uniformity in isoproterenol (ISO)-induced myocardial hypertrophy. 2. Data obtained for isovolumic hearts isolated from 20 rats treated with ISO (0.3 mg/kg over 8 days) were divided into two groups (H1, n = 10; H2, n = 10) according to the volume (mean+/-SD) needed to change left ventricle diastolic pressure from 0 to 40 mmHg (H1, 184+/-30 microL; H2, 108+/-14 microL). Eight control rats (C; 165+/-37 microL) were used for comparison. 3. In addition to ventricular distensibility differences, the groups differed in terms of myocardial mass (mean+/-SEM: H1, 181+/-3 mg > H2, 166+/-3 mg > C, 136+/-3 mg; P < 0.001), of relaxation constant (H2, 43+/-4 msec > H1, 28+/-2 msec; P = 0.0012) and of maximum developed circumferential stress (C, 145+/-9 kdyn/cm2 = H1, 137+/-6 kdyn/cm2 > H2, 110+/-4 kdyn/cm2; P = 0.002). 4. Our results show that ISO-induced myocardial hypertrophy is not homogeneous. Data obtained for H2, taken as a whole and compared with H1 (smaller myocardial mass and impairment of relaxation, elastic stiffness and force generation), suggest that, in some animals, myocardial necrosis and reparative fibrosis may prevail over the stimulus for myocyte growth. The lack of uniformity of ISO-induced myocardial hypertrophy has not been previously reported and may have contributed to the divergence observed in the literature regarding the functional characteristics of the present model.     

DEGRANULATION OF RAT SALIVARY GLANDS FOLLOWING TREATMENT WITH RECEPTOR-SELECTIVE AGONISTS

1. The aim of this study was to find a drug that induces an almost complete degranulation of secretory cells in rat parotid and submandibular glands. 2. Phenylephrine (α-adrenergic), isoproterenol (β-adrenergic) and mecholine (muscarinic cholinergic) were tested. Time and degree of maximal depletion of acinar and granular convoluted tubule cells were determined morphologically. 3. Following phenylephrine-injection (5 mg/kg or 10.2 mg/kg, i.p.), no effect on the acinar granulation level was observed in either of the glands, while about 50–60% granular convoluted tubules were degranulated for at least 120–180 min post-injection. 4. With isoproterenol (5, 10, 40, 70 or 100 mg/kg, i.p.), degranulation of 100% of the acinar cells in the parotid and 80% of the acinar cells in the submandibular gland was observed 90 min post-injection. Granular convoluted tubule cells did not respond to this β-adrenergic drug. 5. Mecholine (3.75 or 7.5 mg/kg, i.p.) induced mainly degranulation of granular convoluted tubule cells (about 50% after 120 min). Numbers of granulated acinar cells decreased only slightly in both glands (about 10%, 90–120 min). 6. From this study it appears that with a relatively low dosage (5 mg/kg, i.p.) of isoproterenol, a high level of degranulation can be induced in acinar cells of rat parotid and submandibular glands without toxic side effects. Concerning granular convoluted tubules, only moderate degranulation was observed with phenylephrine and mecholine, respectively.     

Beta-adrenergic regulation of Sertoli cell adenylyl cyclase: desensitization by homologous hormone

Incubation of Sertoli cell-enriched cultures with D,L-isoproterenol caused a time- and concentration-dependent, homologous desensitization of isoproterenol-responsive adenyl cyclase, whereas the response to FSH was unaffected. Half-maximal desensitization was achieved within 1 h of preincubation, after which a more gradual loss of response was observed. Preincubation of Sertoli cells for 24 h with increasing concentrations of D,L-isoproterenol demonstrated that the concentration required to obtain half-maximal densensitization was approximately 10-fold lower than the Km for activation of adenylyl cyclase. The function of the guanine nucleotide regulatory component (N-component) of the adenylyl cyclase complex in hormonally desensitized Sertoli cells, as evaluated by activation of adenylyl cyclase by GTP, GMPP(NH)P, fluoride and Mg2+, was not affected by the hormone pretreatment. Preincubation of Sertoli cells with a high concentration of dbcAMP (10(-3) M) for 24 h was associated with a 45% reduction in adenylyl cyclase activation by both FSH and isoproterenol. Also in this case fluoride- and GTP-stimulated adenylyl cyclase activities were normal. However, the effects of dibutyryl cyclic AMP occurred much more slowly than agonist-induced desensitization, indicating that cAMP may not be the primary mediator of homologous desensitization of Sertoli cell adenylyl cyclase by isoproterenol.     

Catecholamine modulates nicotinic ACh-receptor sensitivity

The sensitivity of nicotinic acetylcholine (ACh) receptors is modulated by the action of catecholamines in both bullfrog sympathetic ganglion cells and frog skeletal muscle end-plates. According to analyses of the effects of catecholamine on the dose-response curve of the ACh-induced end-plate current and also on the end-plate current (EPC), catecholamines appear to depress the ACh-receptor sensitivity by decreasing the conductance of unit ionic channels of the nicotinic ACh-receptor complex.     

Alterative and plastic insufficiency of cardiomyocytes: isoproterenol-induced damage to myocardium during anthracycline cardiomyopathy

The development of regenerative and plastic myocardial insufficiency induced by anthracycline antibiotic rubomycin is accompanied by a decrease in cardiomyocyte sensitivity to damage produced by synthetic catecholamine isoproterenol. The incidence and the size of coagulation necrosis foci of cardiomyocytes developed 6 h after isoproterenol injection significantly decreased with increasing in the interval between rubomycin injection and subsequent administration of isoproterenol. In Wistar rats receiving rubomycin 3-5 days prior to isoproterenol and exhibiting signs of regenerative and plastic insufficiency, no cardiomyocyte contracture, intracellular myocytolysis, or lump degradation characteristic of cardiac insufficiency induced by endo- and exogenous catecholamines were found.     

Hair growth-modulation by adrenergic drugs

Since we have recently shown that the beta 2-adrenoreceptor (beta 2-AR) expression of selected regions of the hair follicle (HF) epithelium as well as the number of adrenergic nerve fibers in murine skin change in a hair cycle-dependent manner, this has raised the possibility that adrenergic nerves may exert "trophic" functions during HF cycling. To further explore this concept, we have investigated the effect of neuro-pharmacological manipulations on hair growth (anagen) induction in quiescent telogen mouse skin in vivo. Here, we demonstrate that subcutaneous injections of the noradrenaline (NA)-depleting agent guanethidine, or of the neurotoxin 6-hydroxydopamine, but not of the beta 2-AR agonist isoproterenol induce a premature onset of anagen in the lower back skin of C57BL/6 mice. On day 20 after the start of treatment, more than 80% of the guanethidine-treated mice and ca. 65% of the 6-hydroxydopamine-treated (6-OHDA) mice exhibited premature skin darkening and hair growth at the site of drug application, whereas less than one-third of all control animals showed macroscopic signs of anagen development. This was confirmed by histology, demonstrating mature anagen VI HFs only at the immediate site of treatment with guanethidine or 6-OHDA as opposed to resting telogen HFs in the neighboring untreated skin area. This observation further supports the concept that sympathetic nerves are intimately involved in hair growth control and invites one to explore the neuro-pharmacological manipulation of piloneural interactions as a novel therapeutic strategy for the management of hair growth disorders.     

Effect of nicotine aerosol on slowly adapting receptors in the airways of the dog

The response of slowly adapting airway stretch receptors to nicotine aerosol was studied in the paralyzed, artificially ventilated, anesthetized dog. Single-unit stretch receptor recordings were made from individual vagus nerve filaments placed on a pair of platinum hook electrodes. Administration of 2% nicotine aerosol for five consecutive breaths caused an increase in both the peak transpulmonary pressure (Ptp) and in the activity of the slowly adapting stretch receptors (SARs). The results suggest that tracheal SARs were more affected than those receptors located distal to the carina. Administration of nicotine aerosols following pretreatment with isoproterenol, a bronchodilator, failed to significantly increase Ptp and, concomitantly, the activity of SARs. Therefore, the stimulatory effect of nicotine on SARs appeared to involve primarily an indirect activation of SARs via nicotine-induced bronchoconstriction. It is suggested that the activation of SARs may be involved in the reported nicotine-dependent cigarette smoke-induced apnea.     

比较二甲基亚枫及硝苯吡啶对实验性心肌缺血损伤的作用

本文比较了钙拮抗剂硝苯吡啶和羟自由基清除剂二甲基亚枫对异丙肾上腺素性心肌梗塞的作用。结果发现,两者均具有降低心肌脂质过氧化产物丙二醛和游离脂肪酸含量的作用,同时对超氧化物歧化酶、谷胱甘肽过氧化物酶和Ca~(2 )-Mg~(2 )-ATP酶活力显示了一定的效应。文中并进一步分析了Ca~(2 )及羟自由基在心肌缺血中的作用。     

Forskolin- and diacylglycerol-like potentiation of isoproterenol-induced positive inotropic effect in guinea pig papillary muscles by the musk component,musclide

Musclide (ML) is a glycerol-rich mixed component extracted from musk, a dried secretion from the preputial follicle of musk deer, Moschus moschiferus Linn. ML (50 μg/mL) that caused no direct inotropic effect potentiated isoproterenol (Isp)-induced positive inotropic effect in isolated guinea pig papillary muscles. This cardiotonic action has been attributed to β-adrenergic potentiation. The mechanisms were further investigated using pertussis toxin (IAP), cholera toxin (CTX), forskolin (FK) and dioctanoylglycerol (DOG). IAP pretreatment (50 μg/kg, i.p., the 3rd day before tissue isolation) and/or DOG (200 μM, preliminarily applied for 5 min) increased the maximal response of the concentration-response curve for isoproterenol. CTX pretreatment (0.1 μM, for 3 h) increased the affinity. ML (50 μg/mL) or FK (82.9 nM) preliminarily applied for 5 min caused increases in both the maximal response and affinity. The extent of potentiation produced by ML or DOG was not changed in normal muscles or IAP-pretreated muscles. The extent of potentiation by ML was greater in CTX-pretreated muscles than in normal ones. ML or DOG, when combined with FK, caused only the increase in the maximal response. These results suggest that the potentiation mechanisms of ML are partially FK (adenylate cyclase activator)-like and partially DOG (protein kinase C activator)-like.