Alpha-adrenergic receptors in PVT neurons promote recovery from propofol anesthesia / 医学研究生学报

Objective The locus coeruleus noradrenergic system regulates the recovery process of general anesthesia, but its mechanism remains unclear. The locus coeruleus has a large amount of projection to the paraventricular nucleus of the thalamus (PVT). This study was to investigate the effect of the α-noradrenergic receptor in PVT neurons in propofol anesthesia. Methods The immunofluorescence technique was used for comparison of the c-fos expression in the PVT neurons collected from male SD rats under propofol anesthesia (the PA group, n = 4) or no anesthesia (the non-PA group, n = 4) and observation of the activity of PVT neurons. PVT microinjection models were established in 40 rats and randomized into four groups of equal number: noradrenaline, phentolamine, propranolol, and isotonic saline. Under propofol anesthesia, the animals received microinjection of noradrenaline, phentolamine, propranolol, and isotonic saline at 1 μL into the PVT, respectively, and were observed for the time of recovery of righting reflex (RORR) and the δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-25 Hz) and γ waves (25-60 Hz) on EEG before and after microinjection. Results The expression of c-fos was significantly reduced in the PA group compared with that in the non-PA control. The Ca2+ signals in the PVT were significantly increased during the propofol induction of the loss of righting reflex (LORR), but decreased in the early stage of and during propofol anesthesia (P < 0.05), and remarkably increased at the emergence of and during RORR (P < 0.05). In comparison with the isotonic saline control, the noradrenaline group showed markedly shortened time of RORR (837.8 s vs 647.7 s, P < 0.05), reduced rate of δ waves (P < 0.05) and elevated rate of β waves (P < 0.05), while the phentolamine group exhibited prolonged time of RORR (837.8 s vs 1045.1 s, P < 0.05) and increased rate of δ waves after microinjection (P < 0.05). Conclusion The α-noradrenergic receptors in PVT neurons play a critical role in promoting recovery from propofol anesthesia.

Differential effects of saturated and unsaturated fatty acids on vascular reactivity in isolated mesenteric and femoral arteries of rats

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague–Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, 1–10 µM) concentration-dependent contraction was obtained with or without FFAs. Incubation with 100 µM of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with 100 µM of linoleic acid decreased 1 µM PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while 200 µM oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and 2 µM) while increasing it at 10 µM PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.

Síndrome coronario agudo con supradesnivel del ST asociado al feocromocitoma con las catecolaminas inicialmente normales / Acute coronary syndrome with ST elevation associated with pheochromocytoma with initially normal catecholamine values

Los feocromocitomas son tumores secretores de catecolaminas que cursan con paroxismos de hipertensión o hipotensión arterial y palpitaciones. Son una causa rara del síndrome coronario agudo. Presentamos el caso de una paciente con síndrome coronario agudo secundario a feocromocitoma que inicialmente tenía valores normales de catecolaminas.

Pheochromocytomas are catecholamine-secreting tumors that involve paroxysmal hypertension or hypotension and palpitations. They are a rare cause of acute coronary syndrome. We present the case of a patient with acute coronary syndrome secondary to a pheochromocytoma with initially normal catecholamine values.

Tapentadol: Can It Kill Two Birds with One Stone without Breaking Windows?

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the µ-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

Alpha adrenergic receptors in renal pelvis and calyces: can rat models be used?

We aimed, in this study, to determine the distribution of α-1 AR subtypes in rat and human pelvis and calyces, and to evaluate, by comparing these two species, the possibility of rats to be used as models for humans. Twenty patients with renal carcinoma were included into the study. The patients underwent radical nephrectomy for renal cell carcinoma (RCC). After nephrectomy, specimens were evaluated and excisional biopsies from healthy pelvis and calyces tissues were performed. When pathology confirmed the non-invasion of RCC, specimen was included into the study. A total of 7 adult Wistar Albino (250-300 g) female rats were used in this study. Specimens included renal pelvis and calyces. All specimens were evaluated under light microscope histopathologically. The concentrations of the receptor densities did not differ between the two groups. With the demonstration of the α receptors in rat kidneys and calyces, many receptor-based studies concerning both humans and rats can take place. Novel medication targeting these subtypes -in this matter α1A and α1D for renal pelvis and calyces- may be helpful for expulsive therapy and/or pain relief. With the demonstration of similar receptor densities between human and rat tissues, rat model may be useful for α-receptor trials for renal pelvis and calyces.

Modulation of Alpha 1 Adrenergic Receptors on Urinary Bladder in Rat Spinal Cord Injury Model / 대한배뇨장애요실금학회지

PURPOSE: Whereas many studies have focused on the vesical changes of the alpha1 adrenergic receptor (AR) subtypes in partial outlet obstruction, few studies have addressed the modulation of the alpha1 AR subtypes after spinal cord injury (SCI). Therefore, we studied the modulation of the alpha1 ARs in urinary bladder in a rat SCI model. METHODS: Four weeks after a SCI, the whole vesical bodies from eight female Sprague-Dawley rats and from eight controls were harvested. The total RNA was extracted from the samples and was used to prepare cDNA. We developed standard plasmid constructs of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and three alpha1 ARs (alpha1a, alpha1b, and alpha1d) to convert the cycle threshold (Ct) values from real-time polymerase chain reaction (RT-PCR) into subtype mRNA concentrations. The detected Ct values of 16 samples from RT-PCR were interpolated into the standard plasmid curves. RESULTS: All serially diluted standard samples showed very good linearity. The mRNA expression of GAPDH was higher in the SCI group, whereas the mRNA expression of all alpha1 ARs was lower in the SCI group than in the control animals. The alpha1a, alpha1b, and alpha1d mRNA expression in the controls was 81.7%, 3.3%, and 15.1%, respectively, whereas the alpha1a, alpha1b, and alpha1d mRNA expression in the SCI group was 33.5%, 5.2%, and 60.9%, respectively. CONCLUSIONS: SCI moderates the alpha1 AR mRNA subtypes in the urinary bladder. The relatively increased alpha1d or decreased alpha1a AR mRNA expression may be a therapeutic candidate for controlling the symptoms of neurogenic bladder after SCI.

alpha-Adrenoceptor Antagonistic Effect of Palmatine on the Prostatic Urethral Pressure of the Rabbit / 대한비뇨기과학회지

PURPOSE: Palmatine is an isoquinoline alkaloid, with multiple pharmacological actions, including anti-inflammatory activity. The aim of this study was to examine the effect of palmatine on the prostatic urethral pressure in anesthetized rabbit. MATERIALS AND METHODS: 10-week-old male New Zealand White rabbits (3.0-3.5kg) were used in the experiment. After anesthetized with urethane (800mg/kg i.v.), a midline incision was made, and the urinary bladder completely drained. To prevent filling of the bladder, polyethylene tubes were inserted into the bilateral ureters. Using a 3-F MIKRO-TIP catheter transducer positioned in the prostatic urethra, urethral pressure was recorded continuously. To record the blood pressure, the left femoral artery was cannulated with an angiocatheter. After a stabilizing period, phenylephrine (1mug/kg) was intravenously administered two or three times. When the increase in the urethral pressure became stable, palmatine was administered intravenously (0.5-3.0mg/kg), followed by phenylephrine, with no time interval. RESULTS: In the anesthetized rabbits, an intravenous bolus injection of palmatine (0.5-3.0mg/kg) caused no significant change in the resting prostatic urethral pressure (p>0.05), but decreased the blood pressure (p<0.05). After administration of phenylephrine, the urethral pressure increased from 7.5 0.8 mmHg to 26.5 2.6 mmHg, with the difference in the pressure (19.0 3.1 mmHg) being statistically significant (p<0.01). The intravenously administered palmatine (0.5-3.0mg/kg) dose-dependently inhibited the phenylephrine-induced increases in the prostatic urethral pressure and mean blood pressure. The maximal inhibition was obtained when a palmatine dose of 3.0mg/kg was administered, at which point, the decrease in the urethral pressure was 73.1% (p<0.01). CONCLUSIONS: These results indicate that palmatine inhibits the phenylephrine-induced increases in the prostatic urethral pressure and blood pressure in the anesthetized rabbits.

Effect of Isoflurane on Contractile Responses to Norepinephrine in Isolated Thoracic Aortic Vascular Rings of the Rabbits / 대한마취과학회지

BACKGROUND: Volatile anesthetics exert direct depressant and vasodilator effects on vascular smooth muscle. These effects may result in clinically relevant hemodynamic changes. However, the mechanism is not well known whereby volatile anesthetics inhibit the vasoconstrictor actions of catecholamines at vascular smooth muscle. METHODS: The present study examined the direct effects of isoflurane on responses of isolated rabbit thoracic arteries to the norepinephrine(a mixed alpha1- and alpha2-adrenoceptor agonist) and phenylephrine(a selective alpha1-adrenoceptor agonist) applied exogenously. The role of extra- and intracellular Ca2+ in norepinephrine-induced contractions was also examined. RESULTS: Norepinephrine and phenylephrine produced maximal responses of about the same magnitude; however, norepinephrine was more potint than phenylephrine. Isoflurane depressed only the upper portion(10(-5)~10(-4)M) of norepinephrine dose-response curves. The depression of contraction caused by isoflurane on the dose-response curves of norepinephrine and phenylephrine was more marked with phenylephrine than with norepinephrine; isoflurane(2~3%) caused a concentration-dependent attenuatian of the responses evoked by 10(-5) to 10(-3)M phenylephrine. Ryanodine(a selective inhibitor of sarcoplasmic reticulum Ca2+ channels) attenuated the contractile response to norepinephrine. In the Ca2+-free medium the contractile response to norepinephrine was attenuated as compared to control. CONCLUSIONS: Theses results suggest that isoflurane attenuates the contractile responses of isolated rabbit thoracic arteries to norepinephrine and phenylephrine probably interfering with postjunctional alpha1-receptor function.

Studies on characteristics and function of alpha2-adrenoceptors intact lymphocytes isolated from rat spleen / 中国免疫学杂志

~3H-Clonidine, a potent and selective alpha2-adrenergic agonist was used to label alpha2-a-drenoceptors in intact lymphocytes isolated from rat spleen. Binding of ~3H-Clo-nidine was rapid(t1/2: 2min)and readily reversed by 10umol?L~(-1) clonidine(t1/2: 3-4min). ~3H-Clonidine saturationexperiments indicated a single c1ass of site with a K_D of 6.57?1.63nM and Bmax of 72.4?13.4 fmol/10~7 lymphocytes. Adrenergic agonists competed for ~3H-clonidine binding site with anorder of potency:epinephrine)norepinephrine)isoproterenol. These results show the presence ofalpha2-adrenoceptors in splenic lymphocytes. Computer analysis of competition experiments withadrenergic agonists revealed three classes of sites: high affinity site, medium affinity site and lowaffinity site. The affinity of high affinity site is 2-3 orders of magnitude higher than the one ofmedium affinity site, whereas the latter is the same orders higher than low affinity site Using im-proved Mishell-Dutton method, 10umol?L~(-1) clonidine suppressed the Ig M synthesis and thesuppression was blocked by 10 umol?L~(-1) phentolamine. These results indicate the suppression ofIg M antibody response to SRBC in vitro by clonidine is mediated by the alpha-adrenoceptors.