多巴胺和去甲肾上腺素对感染性休克患者肾灌注的影响

目的 研究多巴胺与去甲肾上腺素对感染性休克患者肾灌注的影响.方法 选择ICU早期感染性休克患者44例为研究对象,随机分成多巴胺组(Dopa组)和去甲肾上腺素组(NE组).分别测定并计算应用多巴胺或去甲肾上腺素前(0o)及用药后1 h(T1)、4 h(T2)、8 h(T3)、16 h(T4)、24 h(T5)、48 h(T6)各个时间点的血流动力学指标,测定记录所有患者尿量(UF)、血清肌酐(CCr)、滤过钠排泄分数(FENa)和滤过水排泄分数(FEH2O).结果 与EN组比较Dopa组UF显著增加(P＜0.05),CCr 2组比较差异无统计学意义(P＞0.05);治疗后NE组FEH2O增加(P＜0.05),而Dopa组无明显变化.与Dopa组同一时间点相比NE组的FEH2O明显增加(P＜0.01);治疗后NE组在T4后FENa减少,Dopa组治疗前后无明显变化.T4后和Dopa组同一时间点相比NE组的FENa显著减少(P＜0.05).结论 多巴胺和去甲肾上腺素均能改善感染性休克患者血压、改善肾灌注.去甲肾上腺素对感染性休克合并心动过速及严重组织缺氧的患者是一个比较好的选择.     

Effects of endothelin-1 on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

The effects of endothelin-1 (ET-1) on renal function and norepinephrine (NE) overflow induced by renal nerve stimulation (RNS) were examined in anesthetized dogs, and comparisons were made with effects of Bay K 8644, a calcium channel agonist. RNS at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow and urinary excretion of sodium and increased NE secretion rates without influencing renal hemodynamics. RNS, at a high frequency of 2.5-5.0 Hz which diminishes renal hemodynamics, affected urine formation and NE secretion rate more potently than did low-frequency RNS. Intrarenal arterial infusion of ET-1 (1.0 ng/kg/min) decreased the baseline level of renal blood flow by 25% and that of urinary excretion of sodium by 54-69% but did not alter basal levels of NE secretion rate. During ET-1 infusion, low-frequency RNS-induced antidiuresis was observed to an extent similar to that seen without ET-1 infusion, whereas increase in NE secretion rate elicited by RNS was significantly inhibited by ET-1 infusion (45-65% of the values without ET-1 infusion). In addition, in the case of high-frequency RNS, ET-1 did not affect antidiuretic responses but did inhibit the increase in NE secretion rate by approximately 55%. In contrast, alterations in renal excretory responses and NE secretion rate elicited by RNS were not influenced by Bay K 8644 infusion (1.0 micrograms/kg/min), a dose that decreased renal blood flow to the same degree as did 1.0 ng/kg/min of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine

The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D₂ against LY-171555 (0.05–0.25 mg/kg); but not to the D₁ agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D₁ antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D₂ antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D₁ or D₂ receptor activation; for example, the stimulus properties of this substance might involve both D₁ and D₂ receptor activation.Some of these results were presented at the meeting of the Society for Neuroscience, Toronto, 1988     

Strain-dependent effects of post-training cocaine or nomifensine on memory storage involve both D1 and D2 dopamine receptors

Post-training administration of cocaine (1–10 mg/kg) or nomifensine (1–10 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL16 mice, while impairing it in the DBA/2 strain. The effects on retention performance induced by the psychostimulant and the dopamine (DA) reuptake blocker in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace is susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during the training were not affected by the post-training drug administration. The strain-dependent effects of an intermediate dose (5 mg/kg) of both cocaine and nomifensine were reversed by pretreatment with either selective D₁ or D₂ DA receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D₁ and D₂ receptor types are similarly involved in modulating memory processes. These results show that the effects of cocaine on memory consolidation are related to its dopaminergic action, since they are similar to those produced by nomifensine and, what is more important, are antagonized by pretreatment with DA receptor antagonists. Moreover, they point to possible genotype-dependent factors in DA mediated effects of cocaine on memory consolidation, indicating inbred mice as an experimental tool to investigate neural mechanisms underlying interindividual susceptibility to drug addiction.     

普鲁卡因胺对大心程控刺激电药理学实验模型的作用

用冠脉Harris二期结扎并部分再灌注及吻合支缝扎法造成犬急性前壁心肌梗塞,5～8d后辅以心脏程控刺激技术(PES)进行心电生理检查及复制快速室性心律失常并观察普鲁卡因胺(PA)的电药理作用,PA能显著延长QTc间期,RERP、NERP及IERP,缩小IDR和VDR,抑制心室PES诱发的室速和室颤,表明PA有抗缺血性快速室性心律失常的电药理作用。     

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain.

1. The effects of single-dose regimens of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine (DA) release and metabolism were evaluated in the frontal cortex, hypothalamus, nucleus accumbens and striatum. The regimens selected are known to produce substantial behavioural effects. 2. 3-Methoxytyramine (3MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used to assess DA metabolism by catechol-O-methyltransferase and monoamine oxidase respectively. The rate of formation of 3MT was used as an index of synaptic DA. The ratio and sum, respectively, of 3MT and DOPAC rates of formation were used to assess DA reuptake inhibition and turnover. 3. The effects of amphetamine on 3MT production and DOPAC steady-state levels were similar in all regions, suggesting similar pharmacodynamic actions. Amphetamine increased 3MT formation and steady-state levels, and reduced DOPAC steady-state levels. DOPAC formation was significantly reduced only in the nucleus accumbens and striatum. Total DA turnover remained unchanged except in the nucleus accumbens. Apparently, the amphetamine-induced increase in DA release occurred at the expense of intraneuronal DA metabolism and did not require stimulation of synthesis. 4. Nomifensine elevated 3MT formation in all regions. A similar effect was produced by cocaine except in the nucleus accumbens. GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens. 5. Cocaine selectively reduced DOPAC formation in the frontal cortex. Nomifensine increased and reduced, respectively, DOPAC formation in striatum and hypothalamus. GBR 12909 elevated DOPAC formation in all regions except the cortex, where pargyline did not reduce DOPAC levels in GBR 12909-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of exogenous dopamine: modulation by renal nerves and dopamine receptor antagonists

The modulation of the renal response to exogenous dopamine by renal denervation (DNX) and dopamine receptor antagonists was investigated in thiopental-anesthetized Sprague-Dawley rats. Experiments were performed after reaching stable systemic hemodynamics and urinary flow rate. These conditions were obtained with an infusion rate of approximately 1.2% of body weight per hour. In the vehicle group (VHC) i.v. infusion of dopamine (1, 3 and 9 μg kg^–1 min^–1) significantly increased glomerular filtration rate (GFR), assessed by renal clearance of [³H]inulin, by 14±1.5, 16±1.6 and 31±2.6%, respectively. Infusion of 1 and 3 μg kg^–1 min^–1 dopamine did not change systemic hemodynamics while the highest dose elevated heart rate, potentially contributing to the GFR increase. The specific D₁ receptor antagonist SCH 23390 (10 μg kg^–1 min^–1 i.v.) did not affect the GFR response to dopamine infusion. In contrast, domperidone (DOM; 8 μg kg^–1 min^–1 i.v.), a specific, peripherally acting D₂ antagonist, attenuated the glomerular hyperfiltration induced by the three doses of dopamine to 11±1.7, 13±2.2 and 16±2.6%, respectively. DNX diminished the GFR response to dopamine infusion to almost the same extent (11±2.8, 10±2.2 and 17±2.6%, respectively) as did DOM. When DNX animals were treated with DOM, the GFR responses to dopamine were further attenuated to non-significant increases. These additive effects of DOM and DNX suggest that two different mechanisms are involved. Both DNX and SCH 23390 decreased sodium excretion at baseline whereas DOM enhanced it. Under the present experimental condition, neither D₁ nor D₂ receptor blockade affected the natriuretic and diuretic response to dopamine. Whereas D₁ receptors do not appear to be involved, both D₂ receptors and renal nerves play a role in the renal hemodynamic response to dopamine, indicating involvement of both pre- and postsynaptical dopamine receptors. Received: 19 September 1997 / Accepted: 7 July 1998     

Effects of chronic cocaine self-administration on norepinephrine transporters in the nonhuman primate brain

Rationale While cocaine blocks dopamine and serotonin transporters, considerably less emphasis has been placed on its effects following blockade of the norepinephrine transporter (NET). To date, no studies have made a systematic investigation of the effects of chronic cocaine on primate NET density. Objective We previously reported increases in NET density in portions of the monkey bed nucleus of stria terminalis after 100 days of cocaine self-administration. In the present study we extend these findings and assess the changes in [³H]nisoxetine binding in additional brain regions of rhesus monkeys chronically self-administrating cocaine. Results [³H]Nisoxetine binding sites in the A1 noradrenergic cell group were significantly higher after 5 days of cocaine exposure. One hundred days of self-administration also induced a higher density of NET binding within the A1 cell group; however, in addition, the effects extended to the nucleus prepositus, as well as forebrain regions such as hypothalamic nuclei, basolateral amygdala, parasubiculum, and entorhinal cortex. Conclusions These data demonstrate that cocaine self-administration alters the noradrenergic system of nonhuman primates. Although cocaine affected NET binding sites in the forebrain projections of both the ventral (VNAB) and dorsal (DNAB) noradrenergic bundles, the alteration in the A1 cell group at the early time-point suggests that the VNAB appears to be more sensitive than the DNAB to the effects of cocaine. Given the role of norepinephrine in arousal and attention, as well as mediating responses to stress, long-term exposure to cocaine is likely to result in significant changes in the way in which information is perceived and processed by the central nervous system of long-term cocaine users.     

The role of endogenous angiotensin II in antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

We examined the possible involvement of endogenous angiotensin II (ANG II) in norepinephrine (NE) overflow and antidiuresis induced by renal nerve stimulation (RNS). RNS at a frequency of 0.5-2.0 Hz, which did not influence renal hemodynamics, produced significant reductions in urine flow and urinary excretion of sodium, and elevations in NE secretion rate (NESR) and renin secretion rate (RSR). Intrarenal arterial (i.r.a.) infusion of phentolamine (10 micrograms/kg/min) abolished the RNS-induced antidiuresis. In dogs receiving captopril (15 micrograms/kg/min i.v.), RNS-induced antidiuresis and increase in NESR were significantly attenuated. The i.r.a. administration of propranolol at 5 micrograms/kg/min, a dose that inhibited completely the RNS-induced increase in RSR, did not influence the alterations in NESR and urine formation in response to RNS. During ANG II infusion (1 ng/kg/min i.r.a.), RNS produced a reduction in urine formation and an increase in NESR, at a magnitude similar to that seen without ANG II infusion. These results suggest that RNS at a low frequency increased the NESR and RSR without affecting renal hemodynamics and that the antidiuretic effect was probably produced via the activation of postsynaptic alpha-adrenoceptors, but not via the ANG II receptor, located on the renal tubules. The release of NE appears to be modulated by ANG II through the activation of a facilitatory prejunctional mechanism, which is maximally stimulated by endogenously and locally generated basal levels of ANG II.     

Interaction between norepinephrine release and intrarenal angiotensin II formation during renal nerve stimulation in dogs

We examined possible interactions between intrarenal angiotensin II (ANG II) formation and norepinephrine (NE) release during renal sympathetic nerve stimulation (RNS) in anesthetized dogs. During 10 min of continuous RNS (1.5-2 Hz), the ANG II formation rates (ANG II-FR) and NE secretion rates (NE-SR) were determined at 1 and 10 min. Under control conditions, almost the same extent of increase in the NE-SR was observed at 1 and 10 min of RNS, whereas a significant increase in ANG II-FR was observed at 10 min but not at 1 min. During intrarenal arterial infusion of enalaprilat or losartan, the increase in NE-SR and reduction in renal blood flow at 10 min of RNS were suppressed, whereas the NE release and vasoconstriction responses at 1 min remained unaffected. The RNS-induced increases in ANG II-FR were completely abolished during infusion of enalaprilat. These results suggest that NE release on continuous RNS is enhanced by concomitantly formed ANG II, and this interaction depends on the time-related changes in intrarenal ANG II formation during RNS in the canine kidney.     

Effects of cocaine on extracellular dopamine and serotonin levels in the nucleus accumbens

RATIONALE: Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Patients with schizophrenia have repeatedly been found to show reduced PPI when compared to healthy people. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication in schizophrenic patients. Antipsychotic medication, in particular with atypical drugs, has been shown to improve a range of cognitive functions and normalize PPI deficits in schizophrenia, whereas anticholinergic drugs disrupt cognitive functions in both normal and schizophrenic populations and also impair PPI in experimental animals. No previous study has investigated the effects of anticholinergic drugs on human PPI. OBJECTIVES: This study determined the effects of procyclidine, an anticholinergic drug, on PPI in healthy male volunteers, employing a double-blind placebo-controlled cross-over design. METHODS: Subjects underwent testing for PPI on two occasions: once after the oral administration of a placebo and once after the oral administration of procyclidine in two separate experiments. Experiment 1 examined the effects of 10 mg procyclidine, whereas experiment 2 examined the effects of 15 mg procyclidine. RESULTS: Procyclidine at a 10 mg dose, as compared to placebo, had no effect on PPI, but caused impairments at a 15 mg dose. In both experiments, procyclidine reduced response amplitude over the pulse-alone trials and heart rate 1-2 h post-administration. CONCLUSIONS: PPI of the human acoustic startle response is modulated by procyclidine. The use of anticholinergics needs to be considered in PPI studies in schizophrenia.     

去甲肾上腺素与多巴胺治疗休克的临床疗效及对肾功能的影响比较

目的 比较多巴胺与去甲肾上腺素治疗休克的临床疗效及两者对肾功能的影响.方法 选取休克患者100例,按数字表法随机分为去甲肾上腺素组和多巴胺组,每组50例,接受其他抗休克治疗的同时分别应用去甲肾上腺素和多巴胺进行治疗.观察指标为第7天患者病死率及治疗前、治疗后12 h、72 h的BUN值和肌酐（CRE）值.结果 两组患者第7天的病死率差异无统计学意义（x2=0.765,P＞0.05）.但多巴胺组心律失常发生率为34％,显著高于去甲肾上腺素组的16％（x2=3.84,P＜0.05）.治疗后,两组BUN和CRE均有所恢复,但都略高于正常值,去甲肾上腺素组更接近正常值.结论 应用去甲肾上腺素与多巴胺治疗休克的临床疗效相当,但去甲肾上腺素比多巴胺更能有效地改善肾功能.     

Effects of monoamine releasers with varying selectivity for releasing dopamine/norepinephrine versus serotonin on choice between cocaine and food in rhesus monkeys

Monoamine releasers constitute one class of candidate medications for the treatment of cocaine abuse, and concurrent cocaine-versus-food choice procedures are potentially valuable as experimental tools to evaluate the efficacy and safety of candidate medications. This study assessed the choice between cocaine and food by rhesus monkeys during treatment with five monoamine releasers that varied in selectivity to promote the release of dopamine and norepinephrine versus serotonin (5HT) [m-fluoroamphetamine, (+)-phenmetrazine, (+)-methamphetamine, napthylisopropylamine and (±)-fenfluramine]. Rhesus monkeys (n=8) responded under a concurrent-choice schedule of food delivery (1-g pellets, fixed ratio 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, fixed ratio 10 schedule). Cocaine choice dose-effect curves were determined daily during continuous 7-day treatment with saline or with each test compound dose. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice, and the highest cocaine doses (0.032-0.1 mg/kg/injection) maintained almost exclusive cocaine choice. Efficacy of monoamine releasers to decrease cocaine choice corresponded to their pharmacological selectivity to release dopamine and norepinephrine versus 5HT. None of the releasers reduced cocaine choice or promoted reallocation of responding to food choice to the same extent as when saline was substituted for cocaine. These results extend the range of conditions across which dopamine and norepinephrine-selective releasers have been shown to reduce cocaine self-administration.     

Effects of lithium chloride on norepinephrine and dopamine metabolism in the rat brain]

Lithium chloride (LiCl) was injected acutely (2.4 mEq/kg and 1.2mEq/kg X 2 for 3 hr, i.p.) or subacutely (2.5 mEq/kg X 2/day for 4.5 days, i.p.) in rats, and behavioral effects, steady state levels of norepinephrine (NE), dopamine (DA) and serotonin (5HT) and the metabolism of intraventricularly administered 14C-NE and 14C-DA in the brain were investigated. Acute and subacute administratin of LiCl suppressed the spontaneous motor activity, but had no effect on the levels of NE, DA and 5HT in the brain. Acute administration of LiCl did not influence the total radioactivity and the levels of NE and its metabolites in NE metabolism, while subacute administration of LiCl increased the deaminated metabolites. In DA metabolism, the deaminated metabolites were decreased by acute administration of LiCl and the O-methylated deaminated metabolites were increased by subacute administration. From these results, it is suggested that LiCl stimulates the monoamine oxidase pathway in NE and DA metabolism and the behavioral sedative effects of LiCl are attributed to the reduced functional activity of brain NE and DA neurons.     

Effects of cocaine and norepinephrine on primary cultures of neonatal rat myocardial cells.

Sudden cardiac death associated with cocaine (Coc) abuse in healthy, physically active individuals became a grave concern in the late 1980s. It is well documented that physical activity increases circulating plasma catecholamine levels. Catecholamines as well as Coc are independently capable of inducing toxic cardiac effects. The purpose of this investigation was to evaluate the synergistic or additive toxic effects of norepinephrine (NE) and Coc in primary myocardial cell cultures obtained from 3- to 5-d-old Sprague-Dawley rats. Alterations in lactate dehydrogenase release (LDH), lysosomal neutral red retention (NR), beating activity, and morphology were evaluated after treatment of the cells for 1-24 h with 1 x 10(-3) M Coc alone, 1 x 10(-5) M Coc alone, 1 x 10(-5) M NE alone, 1 x 10(-3) M Coc with 1 x 10(-5) M NE, or 1 x 10(-5) M Coc with 1 x 10(-5) M NE. LDH release was elevated significantly after 24 h only with those cells exposed to 1 x 10(-3) M Coc alone and 1 x 10(-3) M Coc + 1 x 10(-5) M NE. Using NR retention as a score for lysosomal treatment of the cells with 1 x 10(-5) M Coc and 1 x 10(-3) M Coc alone did not decrease dye retention significantly. However, 1 x 10(-5) M NE combined with 1 x 10(-3) M Coc significantly reduced lysosomal dye retention as early as 1 h after treatment. After 24 h, 1 x 10(-5) M NE alone and 1 x 10(-5) M NE combined with 1 x 10(-5) M Coc significantly increased lysosomal fragility. Beating activity was altered in all treatment groups. Contractile activity was slow and irregular or completely absent with 1 x 10(-5) and 1 x 10(-3) M Coc, respectively. When NE (1 x 10(-5) M) was combined with both concentrations of Coc, there was distinct focalization of sharp, rapid contractions within the cells, which were asynchronous and/or arrhythmic in nature. Those cells exposed to 1 x 10(-5) M NE with 1 x 10(-5) M Coc for 24 h appeared hypercontracted with marked pseudopodia and cytoplasmic granule formation distinctly different from that exhibited by the cells exposed to 1 x 10(-5) M Coc alone. These data demonstrate that NE potentiates the adverse effects of Coc on contractile activity and morphology of spontaneously contracting neonatal myocardial cells maintained in culture.     

Responses of the canine hepatic arterial and portal venous vascular beds to dopamine.

Dopamine was injected in graded doses into the hepatic artery of the anaesthetized dog: the typical response was an initial vasoconstriction followed by a more protracted vasodilatation. The vasodilatation was unaffected by propranolol, but was antagonized by haloperidol. The initial hepatic arterial vasoconstriction was inhibited both by haloperidol and by phentolamine. The experiments suggest that the initial vasoconstriction was due to alpha-adrenoceptor stimulation and that the secondary vasodilatation was the result of the stimulation of dopamine receptors. In separate experiments, dopamine was injected into the hepatic portal vein of the dog. The only response seen was a dose-dependent portal vasoconstriction which was antagonized both by haloperidol and by phentolamine. Since both of these antagonists attenuated the portal vasoconstrictor effects of intraportal phenylephrine, it is probable that the portal vasoconstriction effect of dopamine is due to alpha-adrenoceptor stimulation.     

Effects of kappa-opioid receptor agonists on long-term cocaine use and dopamine neurotransmission

kappa-Opioid receptor agonists have been suggested as treatments for cocaine addiction based on studies showing that they block cocaine-related behaviors. To determine the effects of kappa-opioid receptor agonists on long-term behavioral effects associated with cocaine and the neurochemical bases underlying these effects, rats were treated with the selective kappa-opioid receptor agonist U-69593 ((+)(5alpha,7alpha,8beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1 oxaspiro[4.5]dec-8-yl]-benzeneacetamide) alone or in combination with cocaine and locomotor activity was measured daily. In addition, dopamine transporter and dopamine receptor densities were measured using autoradiographic techniques, and tyrosine hydroxylase was measured using immunoautoradiographic techniques. Treatment with U-69593 with or without cocaine decreased locomotor activity. When challenged with cocaine after a 5-day treatment period, the effects of cocaine were markedly reduced in rats initially treated with U-69593 compared to vehicle. When U-69593 was administered five times with 3-day intervals, it alone had no effect on locomotor activity but still reduced activity associated with a cocaine injection. After five daily injections, U-69593 decreased dopamine transporter and dopamine D(2) receptor densities and increased tyrosine hydroxylase levels. These changes were not seen after the 3-day interval regimen, even though cocaine-induced activity was greatly reduced. These findings show that the effects associated with daily U-69593 treatment are attenuated if the drug is administered with a greater interval, while maintaining a blockade of cocaine-induced activity. In addition, U-69593 can block cocaine-induced locomotor effects without major perturbation of the dopamine system.     

Responses of canine coronary arteries to transmural electrical stimulation and nicotine

In helical strips of dog coronary arteries contracted with prostaglandin F_2α, transmural electrical stimulation and nicotine elicited a transient relaxation. The response to electrical stimulation was abolished by tetrodotoxin, bretylium or pretreatment of the dogs with reserpine, and was potentiated by cocaine. Atropine was ineffective. The relaxations were abolished or converted to contractions by sotalol; the contraction was suppressed by phentolamine. The nicotine-induced relaxation was suppressed by hexamethonium, cocaine, bretylium and sotalol. Atropine and tetrodotoxin did not affect the response. Following pretreatment with reserpine, relaxant responses to nicotine were partly reduced; the remaining relaxations were suppressed by atropine, slightly inhibited by sotalol and potentiated by physostigmine. It may be concluded that electrical stimulation liberates norepinephrine from adrenergic nerves, which preferentially activates β-adrenoceptors. The reuptake mechanism appears to function to inactivate liberated norepinephrine. Nicotine-induced relaxations are mediated mainly by liberated norepinephrine; however, as shown by the pretreatment with reserpine, the release of an acetylcholine-like substance may also be involved.