ERKl/2 pathway-mediated norepinephrine regulates function of endothelial progenitor cells / 第二军医大学学报

Objective: To analyze the effects of norepinephrine (NE) on the proliferation and migration of endothelial progenitor cells (EPCs) and the related mechanism. Methods: NE, adrenoceptor antagonist, and MAPK signal pathway blocker of various concentrationswere used to treat peripheral EPCs derived from healthy adults. The proliferation potential, migration capacity and activation of ERK1/2 were assessed after different treatments. Results: NE increased the proliferation potential of EPCs in a dose-dependent manner. The number of EPCs increased by (48.3±23.3)%, (70.5±35.6)%, (82.4±14.9)% and (100. 3±48. 1) % after treatment with NE at 0. 01 μmol/L, 0. 1 μmol/L, 1 μmol/L and 10 μmol/L, respectively. Addition of alpha adrenoceptor antagonist phentolamine, selective beta 2 adrenoceptor antagonist I127, JNK blocker SP600125 and ERK1/2 blocker A6355 could block the above effects of NE, and beta 1 adrenoceptor antagonist metoprolol and p38 blocker PD169318 failed to block the effects of NE. NE at 10 μmol/L significantly promoted the migration of EPCs (P<0. 05). These effects could be blocked by addition of phentolamine (10 μmol/L) and I127 (10 μmol/L), but not by addition of metoprolol. NE(0. 1, 1 and 10 μmol/L) activatedERK1/2 pathway in a dose-dependent manner, which could also be blockedby phentolamine and I127, but not by metoprolol. Conclusion: NE can increase the proliferation potential and migration capacity of EPCs via activating ERK1/2 pathway with alpha and beta 2 adrenoceptor.

Dexmedetomidine in anesthesia of children submitted to videolaparoscopic appendectomy: a double-blind, randomized and placebo-controlled study / Dexmedetomidina na anestesia de crianças submetidas à apendicectomia por videolaparoscopia: um estudo duplo cego randomizado e placebo-controlado

OBJECTIVES: To evaluate the hemodynamic responses to nociceptive stimuli in children submitted to videolaparoscopic appendectomy under balanced anesthesia with isoflurane and dexmedetomidine. METHODS: Randomized, double-blind and placebo-controlled study involving 26 children submitted to videolaparoscopic appendectomy carried out at Hospital São Lucas (PUCRS) between May 2004 and February 2005. Patients were assigned to two groups: (a) Dexmedetomidine group (n=13): infusion of 1µg/kg over 10 minutes and maintenance dose of 0.5µg/kg/h) as an adjuvant to inhaled isoflurane anesthesia; (b) Control group (n=13): normal saline infusion at a similar rate and volume of the dexmedetomidine infusion. During the different surgical and anesthetic periods, groups were compared regarding heart rate, systolic and diastolic arterial blood pressures as well as need of supplemental fentanyl infusion. Student's t test, ANOVA, and Finner's procedure were used for statistical analysis. RESULTS: During the strongest nociceptive stimuli (airway access and abdominal catheter placement), the heart rate and systolic blood pressure increased significantly (p<0.001) in the control group compared to the dexmedetomidine group. Compared to baseline levels, the hemodynamic responses to nociceptive stimuli were more stable when dexmedetomidine was used in combination with inhaled isoflurane anesthesia. The need for supplemental doses of fentanyl and the hemodynamic parameters were similar for both groups. CONCLUSION: Dexmedetomidine combined with inhaled isoflurane for anesthesia of children submitted to videolaparoscopic appendectomy, efficiently blocks the hemodynamic responses to nociceptive stimuli. When compared to placebo, the use of dexmedetomidine did not change the need for supplemental doses of fentanyl for maintenance of hemodynamic parameters during the intraoperative period.

OBJETIVOS: Avaliar a resposta hemodinâmica aos estímulos nocicepticos em crianças submetidas à apendicectomia por videolaparoscopia sob anestesia balanceada com isoflorane e dexmedetomidina. MÉTODOS: Estudo randomizado, duplo cego e placebo controlado envolvendo 26 crianças submetidas à apendicectomia por videolaparoscopia no Hospital São Lucas da PUCRS entre maio de 2004 a fevereiro 2005. Os pacientes foram alocados: a) Grupo Dexmedetomidina (n=13), administrada 1µg/kg em 10 minutos e manutenção de 0,5µg/kg/h como coadjuvante à anestesia inalatória com isoforane; b) Grupo Controle (n=13), que recebia solução fisiológica com volume e velocidade de infusão semelhante ao grupo anterior. Durante os diferentes tempos cirúrgicos e anestésicos os grupos foram comparados em relação à freqüência cardíaca, pressão arterial sistólica e diastólica, assim como necessidade de doses suplementares de fentanil. Os grupos foram comparados pelo teste T, Qui quadrado, a ANOVA e Finner. RESULTADOS: Nos momentos de maior estímulo doloroso (entubação, colocação dos trocateres abdominais), a freqüência cardíaca e tensão arterial sistólica aumentaram significativamente (p<0,001) no grupo placebo em comparação ao grupo dexmedetomidina. Houve maior estabilidade hemodinâmica aos estímulos nociceptivos quando a dexmedetomidina foi empregada na complementação anestésica ao isoforane. A necessidade de doses adicionais de fentanil na manutenção dos parâmetros hemodinâmicos estáveis foi semelhante entre os dois grupos. CONCLUSÃO: A dexmedetomidina, utilizada como coadjuvante ao isoforane na anestesia de crianças submetidas à apendicectomia por videolaparoscopia, bloqueia de forma efetiva a resposta hemodinâmica aos estímulos nociceptivos. No entanto, quando comparada ao placebo a dexmedetomidina não modificou a necessidade de doses complementares de fentanil para manutenção de parâmetros hemodinâmicos estáveis, durante o periodo intraoperatório.

Benign Prostatic Hyperplasia and Alpha Adrenoceptor Blockers / 대한남성과학회지

Benign prostatic hyperplasia (BPH) is the most common disease affecting middle-aged and elderly men. The symptoms of BPH are brought on by enlargement of the prostate by epithelial and smooth muscle cells, urinary obstruction, increased outflow resistance, and unstable detrusor muscle response to obstruction. There are three alpha-1 adrenoceptor (AR) subtypes in prostatic stromal tissue: alpha-1A AR, alpha-1B AR, and alpha-1D AR. Alpha-1 AR blockers relax the prostatic smooth muscle and bladder neck leading to pressure decreases in the bladder and urethra. This treatment improves urinary flow, because 98% of alpha-1 AR is located in the prostatic stroma, and alpha-1 AR is increased in smooth muscle of the enlarged prostate. A selective alpha-1A AR blocker improves obstructive symptoms than irritative symptoms because of the characteristics and distribution of alpha-1A AR and alpha-1D AR in the genito-urinary tract. A combined therapy with selective alpha-1A and alpha-1D AR blockers may improve both voiding and filling symptoms.

Effect of Rilmenidine and Clonidine Premedication on the Cardiovascular Action of Phenylephrine and Nitroprusside in Rats / 대한마취과학회지

BACKGROUND: Patients premedicated with clonidine often present with hypotension and bradycardia. The hypotensive patient premedicated with clonidine should be given a vasopressor to treat hypotension. In these patients, an augmented vasopressor response would be shown. Rilmenidine as an allied drug of clonidine is an antihypertensive agent with selectivity for the imidazoline receptor that acts centrally by reducing sympathetic overactivity. This study was designed to evaluate the effect of clonidine and rilmenidine on changes in mean blood pressure and baroreflex sensitivity following phenylephrine and nitroprusside administration. METHODS: Sixty Sprague-Dawley rats were assigned randomly into one of three groups, control group (n = 20), clonidine group (n = 20) or rilmenidine group (n = 20). Saline (control group), clonidine 30ng/kg (clonidine group) or rilmenidine 300ng/kg (rilmenidine group) were intraperitoneally injected respectively. Following the injection, a phenylephrine and nitroprusside test were performed. RESULTS: The percent change in mean blood perssure from the baseline values in the control group, clonidine group and rilmenidine group were 35 +/- 18%, 54 +/- 17% and 62 +/- 38%, respectively. There was no difference between the baroreflex sensitivity in the pressure (phenylephrine) test (0.94 +/- 0.43, vs 1.05 +/- 0.62, vs 1.13 +/- 0.59 msec/mmHg). In contrast, the slopes of the depressor (nitroprusside) test were decreased in rats receiving clonidine and rilmenidine (0.51 +/- 0.34, vs 0.12 +/- 0.08, vs 0.18 +/- 0.09 msec/mmHg, P < 0.05). CONCLUSIONS: It is concluded that the rilmenidine and clonidine groups showed a more augmented pressure response to vasopressors than the control group. Therefore, the decreased dosage of vasopressors is recommended to treat hypotension in rilmenidine premedicated patients.

Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE (30-100microM) reversibly decreased sIPSC frequency to 41+/-7% of the baseline value (4.4+/-0.8 Hz, p<0.001). This effect was blocked by yohimbine (2-20microM), an alpha2-adrenoceptor antagonist and mimicked by clonidine (50 microM), an alpha2-adrenoceptor agonist. In contrast, NE increased sIPSC frequency to 248+/-32% of the control (3.06+/-0.37 Hz, p<0.001) in 31 of 54 type II neurons, but decreased the frequency to 41+/-7% of the control (5.5+/-1.3 Hz) in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 M omega, p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via alpha2-adrenoceptor, however, either increases in about 60% or decreases in 40% of type II neurons.