甲基莲心碱对兔离体脑基底动脉收缩的影响

为了研究甲基莲心碱对兔离体脑基底动脉收缩的影响及与血管内皮的关系 ,采用离体家兔脑基底动脉环实验方法 ,以苯肾上腺素为兔脑基底动脉环的预收缩剂 ,测定血管张力变化 ,观察甲基莲心碱对血管收缩张力的影响 ;测定血管内皮完整组和去血管内皮组的张力变化 ,观察甲基莲心碱对血管收缩张力的影响是否为血管内皮依赖性的作用。结果发现 :甲基莲心碱抑制苯肾上腺素引起的兔脑基底动脉环收缩的作用与生理盐水对照组比较差异显著 (P <0 .0 0 1 ) ;甲基莲心碱对内皮完整组和对去内皮组血管环的最大舒张百分值分别为 38.4 %± 9.1 %和33.4 %± 1 1 .5 % ,差异无显著性统计学意义 (P >0 .0 5 )。提示甲基莲心碱能抗苯肾上腺素诱导的兔离体脑基底动脉收缩 ,其扩血管的作用主要是其直接松弛血管平滑肌所致     

小剂量去氧肾上腺素静脉泵注在高龄患者髋关节置换手术中的应用

目的观察持续静脉泵注小剂量去氧肾上腺素对高龄髋关节置换手术患者的循环稳定作用。方法36例行髋关节置换手术的高龄患者。术中常规监测血压、心率、ECG和SpO2，记录出血量、输液量、输血量等指标，术后24小时复查肾功能。结果所有患者手术经过顺利，生命体征稳定，术中血压降幅不超过20％，未见严重围手术期并发症。结论高龄患者围手术期持续静脉泵注去氧肾上腺素有助于降低血压下降程度，维持心脑等重要器官的血供，减少心脑血管不良事件的发生，提高麻醉的安全性。     

Baroreceptor Function in the Hypertensive Black African

Hypertension in the black African differs in some respects from white Europeans: complications due to accelerated atherosclerosis are rare and treatment with β-blockers alone is ineffective. It is not known if baroreceptor function is depressed in African hypertensives to the same extent as it is in whites. Therefore, we have assessed baroreceptor reflex sensitivity (BRS) by the phenylephrine method in 19 African hypertensive patients living in the Gambia, West Africa. The results were compared to predicted BRS values for white patients of the same age and blood pressure calculated from a regression equation derived from 61 hypertensive patients studied in Oxford. It was found that baroreceptor reflex sensitivity was reduced in the African hypertensives and the log mean BRS was similar to the predicted value for Europeans of the same age and level of blood pressure (0.473 ± 0.24 msec/mmHg and 0.489 ± 0.21 msec/mmHg respectively). The resting mean arterial pressure in the African patients varied from 117 to 194 mmHg. The results indicated that African hypertensives have a depression of baroreflex sensitivity which is similar to European hypertensive patients.     

蜂毒肽对大鼠主动脉收缩的作用及与钙内流的关系

为探讨蜂毒肽对心血管系统的作用机理,利用离体大鼠主动脉收缩实验及血管平滑肌细胞＾４５Ｃａ内流定量测定方法,观察了蜂毒肽对血管平滑肌的影响。结果发现：蜂毒肽不影响内皮完整主动脉由苯肾上腺素引起的快速收缩,但可溶度依赖地抑制持续收缩;蜂毒肽对去内皮主动脉环由苯肾上腺素引起的收缩无作用;蜂毒肽对内皮完整主动脉未能产生收缩反应,但可使去内皮动脉环产生收缩和＾４５Ｃａ内流增加,卡手普利和苄普地尔能部分拮抗这     

Baroreceptor-heart rate reflex sensitivity enhancement after urinary bladder distention in essential hypertensives

Our objective was to determine if urinary bladder distention modifies the sensitivity of the baroreceptor-heart rate reflex in hypertensive and control subjects. The baroreceptor-heart rate reflex sensitivity was measured in 15 male patients (mean age 37 ± 8 years) with mild untreated hypertension (mean 163 ± 8/95 ± 12 mmHg) and 17 age- and sex-matched control subjects before and after urinary bladder distention. Bladder filling was performed infusing saline heated to 37°C via a urinary catheter; the volume infused in each patient corresponded to that which caused the urge to void without reaching the pain threshold. The baroreceptor-heart rate reflex sensitivity was determined correlating the variations of the systolic pressure and of the peak blood flow velocity in the common carotid artery with the variations of the ECG RR′ interval of the following heart beat, both during spontaneous and phenylephrine-induced fluctuations of the haemodynamic variables. After bladder distention the diastolic pressure of the hypertensive subjects increased significantly (95 ± 12 vs. 100 ± 12 mmHg; P < 0.02), whereas the heart rate decreased (RR=873 ± 70 vs. 926 ± 80 ms; P < 0.005). These parameters were unchanged in the normotensive subjects (84 ± 9 vs. 83 ± 8 mmHg and 914 ± 158 vs. 913±140 ms, respectively). The baroreceptor-heart rate reflex sensitivity, measured on the basis of spontaneous pressure and carotid blood flow velocity fluctuations in relationship to RR changes, decreased in the normotensive subjects after bladder distention (10.7 ± 4.6 vs. 9.4 ± 2.7 ms/mmHg; P < 0.05 and 423 ± 99 vs. 356 ± 102 ms/kHz; P < 0.01, respectively), whereas it increased in the hypertensive patients (6.9 ± 3.6 vs. 8.3 ± 2.8 ms/mmHg; P < 0.03, and 332 ± 86 vs. 381 ± 97 ms/kHz; P < 0.03 respectively). After bladder distention and phenylephrine administration the baroreceptor-heart rate reflex sensitivity, measured by the correlation between systolic pressure and RR interval, increased only in the hypertensive group (10.2 ± 5.4 vs. 15.2 ± 7.7 ms/mmHg; P < 0.005). In conclusion urinary bladder distention provokes in hypertensives but not normotensive controls a brisk parasympathetic response of the component of the baroreceptor-heart rate reflex which controls heart rate. Received: 17 June 1998 / Accepted: 20 October 1998     

A role for presynaptic α2-adrenoceptors in angiotensin II-induced drinking in rats

Studies from this laboratory have shown that either central or peripheral administration of clonidine, the α₂-adrenoceptor agonist, can attenuate a variety of dipsogenic stimuli in rats. Further, yohimbine and tolazoline, α₂-adrenoceptor antagonists, augment the drinking response to both peripherally administered isoproterenol and angiotensin II. Studies reported here establish a dose-inhibition relationship between the dose of clonidine administered (2 to 32 μg/kg) intracerebroventricularly (IVT) and inhibition of the drinking response to peripherally administered angiotensin II (200 μg/kg, SC). DI₅₀ was approximately 4 μg/kg. Yohimbine (300 μg/kg, SC) reversed the antidipsogenic effect of centrally administered clonidine (32 μg/kg, IVT) on angiotensin II-induced (200 μg/kg, SC) water intake. Phenylephrine, an α₂-adrenoceptor agonist, administered IVT (40 and 80 μg/kg) also inhibited angiotensin II-induced drinking in a dose-related fashion. The antidipsogenic effect of phenylephrine (80 μg/kg) was blocked by administration of yohimbine (300 μg/kg, SC). Thus, this effect of phenylephrine most likely occurs by way of α₂-adrenoceptors. These results support a role for the pre-synaptic α₂-adrenoceptor in the mediation of drinking in rats. Activation of α₂-adrenoceptors is accompanied by reduced water intake while inhibition of these receptors enhances water intake.     

Alpha-adrenoceptor-mediated chronotropic response: influence of temperature and basal spontaneous rate

Summary The chronotropic response to phenylephrine of isolated rat atria was determined at 37°C and 30°C. At both temperatures similar maximal increases in rate were obtained (91 +- 4 beats/min and 93 +- 8 beats/min, respectively). Beta-adrenoceptor blockade (10^–6 M propranolol) abolished the chronotropic effect of phenylephrine at 37°C whereas at 30°C a propranolol-resistant chronotropic effect was detected. The propranolol-resistant chronotropic effect of phenylephrine was sensitive to prazosin blockade (10^–6 M) indicating alpha adrenoceptors involvement in the response. At 37°C a propranolol-resistant, prazosin-sensitive effect of phenylephrine could be obtained if basal rate was lowered (by cholinergic stimulation or acidosis) or if extracellular calcium was increased over 1.35 mM. When the chronotropic effect of phenylephrine was compared at similar basal rates, it was greater at 37°C than at 30°C. These results make unlikely the possibility of increases in sensitivity or in density of alpha-adrenoceptors at low temperature. The fact that alpha-adrenoceptor mediated chronotropic response is enhanced at low basal frequencies makes this mechanism a potential safety factor during bradycardia.Members of Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina Send offprint requests to M. C. Camilion de Hurtado at the above address     

Antinociceptive interactions between intrathecally administered α noradrenergic agonists and′5-N-ethylcar☐amide adenosine

Recently, it has been shown that intrathecal injection of norepinephrine and the mixed A₁/A₂ adenosine agonist5′-N-ethylcar☐amide adenosine (NECA) interact in a supra-additive manner to produce antinociception. The present studies were designed to determined whetherα₁orα₂ noradrenergic receptors are involved in producing the antinociception induced by NECA and norepinephrine. The results indicated that intrathecal injection of NECA (0.97–4.9 nmol), theα₂ noradrenertic agonist clonidine (3.8–375 nmol), or theα₁ agonist phenylephrine (4.9–73.4 nmol) produced dose-dependent antinociception in rats. Furthermore, intrathecal injection of subeffective doses of NECA and clonidine interacted supra-additively to produce potent antinociception. In contrast, no supra-additive interaction was observed between NECA and phenylephrine. The supra-additive interaction of NECA and clonidine did not appear to result from alteractions in cardiovascular tone because changes in blood pressure and nociceptive thresholds were not correlated in time. These results suggests that the noradrenergic component of the supra-additive interaction between adenosine A₂ receptor agonists and noradrenergic agonists is mediated byα₂ noradrenergic receptors.     

An analysis of the inhibitory effects of prazosin on the phenylephrine response curves of the rat aorta

Summary On the endothelium-intact rat aorta some studies have shown prazosin to cause nonparallel rightward shifts of ₁-adrenoceptor agonist response curves. The aim of the present study was to analyze the inhibitory effect of prazosin on the phenylephrine responses of the endothelium-intact and endothelium-denuded rat aorta. Firstly I used phenoxybenzamine treatment to characterize the phenylephrine responses. The K_A values for phenylephrine were 0.13–0.18 M and 0.07–0.16 M in the endothelium-intact and endothelium-denuded rat aorta, respectively. In order to produce maximal responses of the endothelium-intact or — denuded preparation, phenylephrine had to occupy 95–99% of the ₁-adrenoceptors.Secondly I compared the inhibitory effects of phentolamine and prazosin on the endothelium-intact rat aorta. Phentolamine at 0.1 and 1 M caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses (phentolamine pA₂ = 7.9). The inhibitory effects of phentolamine were readily reversible. Prazosin at 0.1–10 nM caused nonparallel rightward shifts of the phenylephrine response curves with a depression of the maximal response. These inhibitory effects of prazosin were either irreversible or only very slowly reversible in drug-free solution and slowly reversible in the presence of phentolamine. Ninety min was required for the inhibitory effect of prazosin to reach equilibrium whereas phentolamine was at equilibrium after 45 min. Finally I have characterized the inhibitory actions of prazosin on the endothelium-denuded rat aorta. Prazosin caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses. The inhibitory effects of prazosin were at equilibrium after 45 min and were readily reversible.In conclusion prazosin is a readily reversible ₁-adrenoceptor antagonist in the endothelium-denuded but not in the endothelium-intact rat aorta. It seems likely that the endothelium accumulates or binds prazosin strongly so that the inhibitory action of prazosin is apparently slowly reversible in the endothelium-intact rat aorta.     

Inhibition of the adrenalectomy-induced increase in plasma renin concentration by vasoconstrictor agents in rats

Summary Plasma renin concentrations in rats increase after bilateral adrenalectomy without sodium substitution. The effects of i.v. infused (asp¹--amid, val⁵)-angiotensin II (1 g/kg min), felypressin (phen², lys⁸-vasopressin) (40 mU/kg min) and phenylephrine (30 g/kg min) were investigated on the increase in plasma renin concentration. These effects of the agents were compared with their actions on blood pressure, heart rate and renal hemodynamics.In rats with destroyed macula densa cells the effect of bilateral adrenalectomy without sodium substitution was also studied. Adrenalectomy still increased the plasma renin concentration. Angiotensin II and felypressin, also depressed under these conditions the elevation of plasma renin concentration caused by adrenalectomy.The mechanism of the adrenalectomy-induced reinin release and its suppression by vasoconstrictor agents is discussed.Supported by DFG Me 541/1