CHARACTERISTICS OF THE DOPAMINE RECEPTORS INVOLVED IN THE ANORECTIC EFFECTS OF APOMORPHINE IN MICE

In food-deprived mice apomorphine injected SC induced a brief (15-30 min) dose-dependent (30-150 micrograms/kg) reduction in food intake. This effect occurred in naive mice as well as in mice habituated to a food deprivation procedure. The anorectic effect of apomorphine (150 micrograms/kg SC) was antagonized by sulpiride (ID50 = 8.6 mg/kg) and by haloperidol (ID50 = 66 micrograms/kg) but domperidone was ineffective (250 micrograms/kg). Mice submitted to a semi-chronic (6 d) blockade of dopamine receptors by haloperidol or injected intracerebroventricularly with 125 micrograms 6-hydroxydopamine 21 d before testing failed to develop a hypersensitivity to the anorectic effect of apomorphine (60 micrograms/kg). Although a single apomorphine injection (5 mg/kg) induced tolerance to the hypothermic effect of a second apomorphine injection of 150 micrograms/kg, it did not modify the anorectic effect. Repeated apomorphine injection (5 x 5 mg/kg) resulted in a slight but significant reduction in apomorphine-induced anorexia. A similarly significant reduction was not observed in mice submitted to repeated injections of dexamphetamine (5 x 5 mg/kg).     

多巴胺D_2受体激动剂和拮抗剂对缺血后海马CA1区神经元凋亡的影响

目的 :研究多巴胺D2 受体激动剂和拮抗剂对沙土鼠前脑缺血再灌注损伤海马CA1区神经元凋亡的影响。方法 :采用沙土鼠双侧颈总动脉阻断 5min缺血再灌注模型。 2 4只沙土鼠随机分为假手术组 (Sham )、缺血组 (I -R)、D2 受体激动剂组 (I -PER)及D2 受体拮抗剂组 (I -SPI)。于再灌注第 7d行开阔法行为学检查、组织病理学检查及TUNEL法检测海马CA1区凋亡锥体细胞数。结果 :5min前脑缺血再灌注 7d可引起沙土鼠海马CA1区约 95 %的锥体细胞凋亡。行为学结果显示I -R组鼠探索活动较Sham组明显活跃 (P <0 0 1) ) ,I -PER组鼠的探索活动较I -R组明显减弱 (P <0 0 1)。组织病理学结果显示I -PER组海马CA1区存活锥体细胞计数明显多于I -R组 (P <0 0 1)。TUNEL法检测发现 ,与Sham组相比 ,其余 3组海马CA1区凋亡细胞数均增多 (P <0 0 5 )。I -PER组海马CA1区凋亡细胞数显著低于I-R组 (P <0 0 5 )。结论 :D2 受体激动剂可显著抑制沙土鼠前脑缺血再灌注损伤海马CA1区神经元凋亡 ,提高存活细胞数 ,改善行为学障碍。     

Hypotensive action of bromocriptine in the DOCA-salt hypertensive rat: Contribution of spinal dopamine receptors

Summary— To assess the role of spinal dopamine receptors in mediation of hypotension induced by systemic administration of the dopamine D₂ receptor agonist, bromocriptine, conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rats were pretreated with either intravenous (iv; 500 μg/kg) or intrathecal (it; 40 μg/rat at T₉-T₁₀) domperidone, a selective dopamine D₂ receptor antagonist that does not cross the blood-brain barrier. In DOCA-salt hypertensive rats, iv administration of a sub-maximal dose of bromocriptine (150 μg/kg) induced a significant decrease in mean aortic pressure (MAP) which was greater and longer lasting than that in uninephrectomized control rats. Intravenous or it pretreatment with domperidone reduced partially, but significantly, the hypotensive effect of bromocriptine (reduction of about 57% and 45% of the maximal effect, respectively). The remaining responses observed during the 60 min postinjection period were still statistically significant as compared with vehicle injection. In contrast, the bromocriptine-induced hypotension was fully abolished by iv pretreatment with metoclopramide (300 μg/kg), a dopamine D₂ receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with iv and it domperidone. These results suggest that, in DOCA-salt hypertensive rats, the hypotension induced by iv bromocriptine is mediated partly through a peripheral D₂ dopaminergic mechanism and partly through stimulation of spinal dopamine D₂ receptors, as has been demonstrated in conscious normotensive rats.     

CLINICAL EVALUATION OF THE CARDIOVASCULAR EFFECTS AND THE PHARMACOKINETICS OF BENALFOCIN AND ITS METABOLITE IN HEALTHY SUBJECTS DURING REPEATED DOSING

The cardiovascular effects and the pharmacokinetics of a new selective alpha-2 adrenoceptor antagonist, benalfocin, and its active metabolite, both compounds with a similar receptor affinity profile, were examined in healthy volunteers during repeated dosage. Significant diastolic blood pressure lowering effects were observed on the first and the last day of the treatment persisting throughout the dosage interval. Furthermore, heart rate reductions were found on these days which were significantly correlated with both the parent compound's and the metabolite's plasma concentrations and their sum. Pharmacokinetics remained unchanged after a 1-wk oral dosing as compared to a single oral dose; the plasma half-life of the metabolite was 3-fold longer than that of the parent compound. In normotensive subjects, benalfocin produced blood pressure and heart rate reducing effects, the latter being more correlated with the metabolite's plasma concentrations. Furthermore, results suggest that the compound's known cholinergic effects may be particularly related to the metabolite and that this molecule is an interesting cardiovascular compound.     

CARDIOVASCULAR EFFECTS FROM STIMULATION OF 5-HYDROXYTRYPTAMINE RECEPTORS

The cardiovascular effects of 5-hydroxytryptamine (5-HT), consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilatation or vasoconstriction, are mediated by three main types of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In intact animals 5-HT elicits a short-lasting bradycardia, accompanied by hypotension, via stimulation of 5-HT3 receptors located on sensory vagal nerve endings in the heart (Bezold-Jarisch reflex). The nature of 5-HT receptors mediating tachycardiac responses is species-dependent. Myocardial 5-HT1-like and 5-HT2 receptors subserve tachycardia in the cat and rat, respectively. Tachycardia in the dog and rabbit is due to a release of catecholamines effected via the 5-HT2 receptors on the adrenal medulla and the 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibres, respectively. The receptors mediating tachycardia in the pig are unique as they do not resemble any of the three 5-HT receptors characterized so far. The blood pressure response to 5-HT is usually triphasic: initial short-lasting hypotension due to reflex bradycardia (via 5-HT3 receptors), a middle pressor phase (via 5-HT2 receptors), and a longer-lasting hypotension (via 5-HT1-like receptors). Vascular contraction by 5-HT is generally mediated by 5-HT2 receptors (located primarily on the large conducting vessels), though in some instances (e.g., dog saphenous vein, dog and human basilar artery, and porcine arteriovenous anastomoses) the contractile response is (also) mediated via 5-HT1-like receptors. Venous dilatation and arteriolar dilatation (leading to increased capillary ['nutrient'] blood flow) occur via 5-HT1-like receptors located mainly on the vascular smooth muscles but also on the endothelium; the smooth muscle and endothelial 5-HT1-like receptors seem to be heterogeneous. In addition, 5-HT can elicit vasodilatation and hypotension as a result of decreased sympathetic nervous tone by acting within the central nervous system and by inhibiting noradrenaline release by a presynaptic action. Both these effects also involve 5-HT1-like receptors that do not appear to be identical. Last, knowledge of the cardiovascular effects of 5-HT and the nature of the receptors involved should be helpful in developing 5-HT-related compounds that may be useful in the treatment of hypertension, migraine, and peripheral vascular diseases.     

LACK OF EVIDENCE FOR AXONAL TRANSPORT OF D1 AND D2 RECEPTORS IN THE NIGRO-STRIATAL PATHWAY OF THE RAT

The possibility that D1 and D2 dopamine receptors are axonally transported in the nigro-striatal pathway has been investigated in the rat by placing a coronal knife cut (sparing the striato-nigral pathway) through the medial forebrain bundle (MFB) and autoradiographically examining the density of D2 (as labeled by [3H]spiperone in the presence of ketanserin) and D1 (as labeled by [3H]SCH 23390) receptors. The efficacy of MFB transection has been assessed by measuring in parallel the binding of [3]ketanserin, a ligand that has been reported to be axonally transported in this bundle. At 12 h post-transection, there was a minor accumulation of [3H]spiperone binding on both sides of the transection. However, (+)butaclamol (1 microM) failed to displace the ligand build-up at the knife cut, thus demonstrating the nonspecific nature of [3H]spiperone accumulation. Similar results were observed at 24, 48, and 72 h after severing the MFB. MFB transection also failed to cause changes in specific [3H]SCH 23390 binding at the knife cut at 12-72 h post-surgery. In contrast, a dramatic accumulation of [3H]ketanserin binding sites was observed rostral and caudal to the cut at 12 h post-transection, attesting to the efficacy of the lesion. These results confirm the existence of both anterograde and retrograde transport of [3H]ketanserin binding sites and suggest that D1 and D2 receptors are not axonally transported in fibers of the nigro-striatal pathway.     

Effects of isometric handgrip training on cardiac autonomic profile: A systematic review and meta‐analysis study

Meta‐analyses have shown that isometric handgrip training reduces blood pressure in normotensive and hypertensive subjects. However, the effects on cardiac autonomic modulation are still controversial. Thus, the aim of this systematic review and meta‐analysis was to analyse the effects of isometric handgrip training on cardiac autonomic modulation in normotensive and hypertensive subjects. For this, Medline, Cinhal, Embase, Spordiscus and PEdro were searched for relevant studies published until December 2018. Randomized controlled trials investigating the effect of isometric handgrip training on heart rate variability parameters were considered eligible. Parameters were obtained in time (standard deviation of all the RR intervals‐SDNN, root mean square of successive differences between the normal adjacent RR intervals‐RMSSD and the percentage of adjacent intervals with more than 50 ms‐PNN50) and frequency domain (low frequency‐LF, high frequency‐HF and sympathovagal balance‐LF/HF). Mean difference (MD) and 95% confidence interval (95% CI) were calculated using an inverse variance method with a random effects model. Seven trials were included in the systematic review and meta‐analysis, totalling 86 participants. No significant effect was observed in heart rate variability parameters after isometric handgrip training (4 trials to SDNN: MD = ?1.44 ms and 95% CI = ?8.02, 5.14 ms; RMSSD: MD = ?1.48 ms and 95% CI = ?9.41, 6.45 ms; PNN50: MD = 0.85% and 95% CI = ?1.10, 2.81%; 7 trials to LF: ?0.17 n.u. and 95% CI = ?6.32, 5.98 n.u.; HF: MD = 0.17 n.u. and 95% CI = ?5.97, 6.30 n.u.; and LF/HF: MD = 0.13 and 95% CI = ?0.34, 0.59). In conclusion, current literature indicates that isometric handgrip training does not improve heart rate variability.     

Cluster Headache: Cardiovascular Responses to Head-up Tilt

Head-up tilt tests were performed in six cluster headache patients in a bout of attacks, but in a pain-free interval at the time of investigation; and in eleven controls matched for age, basal blood pressure, and heart rate. A Doppler servomethod was used for a noninvasive, beat-to-beat blood pressure determination. There were no significant differences between the cluster headache and control groups for heart rate and systolic blood pressure response to the head-up tilt. However, the average diastolic blood pressure seemed to drop more after the tilt in the cluster headache group than in the control group; in particular, in the later part of the test. This might suggest a dysfunction of the baroreflex in cluster headache patients in a bout, also outside of attacks, and most probably of the sympathetically-mediated vasomotor response.     

手术体位对患者术中生理心理影响的观察研究

目的 通过对4种最常见的手术体位观察,总结手术体位护理的体会。方法 通过对4种手术位过程中患心率、呼吸、血压变化及不适焦虑评分APAIS的变化,分析4种体位对患术中生理、心理的影响。结果 4种手术体位中侧卧位和俯卧位时的患的心率、呼吸、血压变化等程度最大,APAIS不适焦虑评分变化差亦最大。结论 侧卧位和俯卧位是手术病人较难接受的体位,要求手术护士加强手术过程中体位护理工作。     

Cluster headache: alterations in heart rate, blood pressure and orthostatic responses during spontaneous attacks

Changes in heart rate and blood pressure (BP) have been monitored beat-to-beat in a cluster headache patient with and without attacks using a non-invasive Doppler servo method. Two attacks were monitored and during one of them a tilt test was carried out. The variability of heart rate and BP was greater during the attack than during the interparoxysmal period. A marked bradycardia occurred during attacks. Systolic BP increased slightly. There was no heart rate increase after tilting during the attack, whereas this was present invariably during tests carried out interparoxysmally. BP changes during "attack tilt" were difficult to evaluate because of large variation. This may be the first observation of a baroreflex arc dysfunction during a cluster headache attack.     

冠心病和糖尿病患者餐后血压及心率变化的研究

目的研究冠心病(coronaryatherosclerolicheartdisease,CD)和2型糖尿病(diabetesmellitus,DM)患者餐后血压和心率的变化特点。方法按疾病种类将187例患者分为3组,即冠心病组(CD,71例),2型糖尿病组(DM,49例),冠心病伴2型糖尿病组(CD+DM,67例)。观察各组24h动态血压和心率,以及进标准定量饮食前后收缩压(systolicbloodpressure,SBP)、舒张压(diastolicbloodpressure,DBP)和心率的变化。结果CD组和CD+DM组24h平均收缩压和24h平均舒张压较DM组明显增高(P<0.01),而DM组和CD+DM组24h平均心率较CD组快(P<0.01);CD组在餐后30～60min的SBP、DBP和心率较餐前对应时间点升高(P<0.01),餐后90min的SBP、DBP和心率恢复至餐前水平。DM组和CD+DM组在餐后30～90min的SBP、DBP和心率下降(P<0.01),餐后120min的SBP、DBP和心率恢复至餐前水平。结论冠心病和2型糖尿病患者餐后血压和心率的变化有不同的特点,表现为冠心病患者餐后血压升高和心率增快,而2型糖尿病或伴冠心病的2型糖尿病患者餐后血压和心率下降,且其血压和心率恢复至餐前水平较单纯糖尿病患者慢。     

EFFECTS OF CHRONIC EXCESS SALT INGESTION : GENETIC INFLUENCE ON THE DEVELOPMENT OF SALT HYPERTENSION IN PARABIOTIC RATS: EVIDENCE FOR A HUMORAL FACTOR

Parabiosis has been found to modify the expected blood pressure response of rats from two strains with opposite genetic propensities for experimental hypertension. When a member from one strain was united in parabiosis with a member from the other and both were maintained on high NaCl diet, the rat from the strain ordinarily resistant to it rapidly developed hypertension, in contrast to appropriate controls from this strain. The development of hypertension in this resistant animal preceded that in its mate from the strain highly sensitive to hypertension. In the latter, both the level of hypertension and mortality were significantly less than in its control. It seems likely that the hypertension observed is the resistant parabiont was initiated in its partner from the sensitive strain. This modification in blood pressures was not observed in the absence of a high NaCl diet. Parabiosis between animals from the same strain did not alter their response. Thus, as in earlier experiences (1–4) the interaction of a nongenetic factor (NaCl) with the appropriate genetic substrate appeared to be necessary for the development of hypertension. The findings are interpreted as evidence that a transmittable humoral influence plays an important role in the pathogenesis of rat hypertension. The presence of this agent is genetically determined but, under the conditions of these experiments, it took the added stimulus of dietary NaCl to demonstrate its existence.     

Heart rate and blood pressure variability in cardiac diseases: pharmacological implications

Summary— Even at rest, blood pressure and heart rate fluctuate continuously around their mean values. Considerable interest has recently focused on the assessment of spontaneous fluctuations in heart rate and blood pressure, ie, heart rate and blood pressure variability, using time or frequency domain indexes. Heart rate variability has been extensively studied in cardiovascular disease and has emerged as a valuable parameter for detecting abnormalities in autonomic cardiovascular control, evaluating the prognosis and assessing the impact of drug therapy on the autonomic nervous system in patients with myocardial infarction, congestive heart failure or a heart transplant. In contrast, until the recent development of noninvasive methods for continuous blood pressure recording, blood pressure variability received little attention, and this parameter remains to be evaluated in cardiovascular disease.     

MECHANISM OF ACTION OF MIGRATION INHIBITORY FACTOR (MIF) : I. EVIDENCE FOR A RECEPTOR FOR MIF PRESENT ON THE PERITONEAL MACROPHAGE BUT NOT ON THE ALVEOLAR MACROPHAGE

The initial interaction between migration inhibitory factor (MIF) and the guinea pig alveolar and peritoneal macrophage was studied. MIF-containing supernatants were generated from sensitized lymph node lymphocytes obtained from guinea pigs immunized with bovine gamma globulin in complete Freund's adjuvant. MIF-containing supernatants were markedly inhibitory for the migration of the peritoneal macrophage but had no effect on the alveolar macrophage. A linear relationship was observed between per cent inhibition of migration and serial twofold dilution of supernatant. Reexpressed in arbitrary MIF units, this relationship reflects a dose-response relationship with saturation characteristics. Pulse exposure of peritoneal macrophages to MIF resulted in adsorption of MIF onto both viable and nonviable cells with corresponding depletion of supernatant MIF. The alveolar macrophage did not adsorb MIF. Pulse adsorption of MIF onto the peritoneal macrophage is dependent on time, temperature, and cell number. Pretreatment of the cells with proteolytic enzyme prevents the adsorption of MIF while leaving migration unaffected. These observations support the existence of a specific cell surface receptor for MIF. The existence of such a receptor provides selectivity of immune modulation of macrophage populations by lymphocytes in delayed hypersensitivity reactions.     

机械通气病人实施音乐干预的效果研究

[目的]了解音乐干预降低机械通气病人焦虑水平以及稳定机械通气病人生理指标的效果.[方法]将150例机械通气病人随机分为音乐组、耳机组、空白组,采用中国版状态-特质焦虑量表(C-STAI)对3组病人干预前后的焦虑水平进行测试,定时记录心率、呼吸和血压.[结果]音乐组、耳机组干预前后C-STAI得分差值差异均有统计学意义(P＜0.001);音乐组干预前后心率、呼吸、收缩压和舒张压变化均有统计学意义(P≤0.001).[结论]音乐干预与戴耳机均有降低机械通气病人焦虑水平的作用,且音乐的作用更显著;音乐可以稳定机械通气病人心率、呼吸、血压.     

INHIBITORY AND STIMULATORY EFFECTS OF CONCANAVALIN A ON THE RESPONSE OF MOUSE SPLEEN CELL SUSPENSIONS TO ANTIGEN : II. EVIDENCE FOR SEPARATE STIMULATORY AND INHIBITORY CELLS

The addition of concanavalin A to mouse spleen cell suspensions can either inhibit or stimulate the immune response to heterologous erythrocytes according to the experimental conditions. Evidence is presented which is incompatible with the hypothesis that these two effects are mediated by a single cell and which favors the hypothesis of separate inhibitor and stimulatory cells.     

LIMITATIONS OF THE BENZODIAZEPINE RECEPTOR NOMENCLATURE: A PROPOSAL FOR A PHARMACOLOGICAL CLASSIFICATION AS OMEGA RECEPTOR SUBTYPES

At present, the nomenclature of benzodiazepine (BZ) receptors is based on historical association with the BZ structure. However, it is mainly through the new compounds chemically unrelated to BZ that the central and peripheral subtypes of BZ receptors have been characterized. We therefore propose the nomenclature of a Greek letter omega, as omega 1, omega 2, and omega 3 to designate the central BZ1, BZ2, and peripheral BZ receptors, respectively. Among the several classes of non-BZD drugs with affinity for different receptors, the imidazopyridines provide a valuable tool for the characterization of omega receptor subtypes. Most BZ are nonselective ligands for the central omega 1 and omega 2 receptors, while selectivity for omega 1 receptor subtypes is present in several non BZ chemical series: imidazopyridines (zolpidem), triazolopyridazines (CL 218872), betacarbolines (beta-CCE), and pyrazoloquinolines (CGS 8216). Selective ligands for the omega 2 subtype are not available so far. The so-called peripheral BZ receptor is also present in the central nervous system; therefore, the proposed nomenclature of omega 3 receptors resolves this paradox because it does not designate location and is defined in terms of pharmacological specificity. Selective ligands for omega 3 receptors include the BZ Ro 5-4864, and the isoquinolinecarboxamide PK 11195, while the imidazopyridine alpidem is the ligand with the highest affinity for this receptor subtype.     

Cluster headache: Heart rate and blood pressure changes during spontaneous attacks

The ECG findings before, during and following 81 spontaneous attacks of cluster headache in 24 patients have been recorded using a Holter cardiography system. No significant change in mean heart rate was found during attacks, when all attacks were considered as a group. Attacks which began when patients were awake differed from those which began during sleep as regards changes in mean heart rate. The mean heart rate decreased during the majority (61%) of attacks which began when patients were awake, whereas it remained unchanged or increased during the majority (67.5%) of attacks which began during sleep. The attacks which began when patients were awake also had higher absolute mean heart rate values before, during and following attacks compared to similar values for those attacks which began during sleep. Blood pressure was measured during 11 attacks and showed a significant increase in both systolic and diastolic blood pressure. The heart rate and blood pressure in six patients usually increased during induced head pain.