Effects Of Adrenergic Agonists Research Articles

Long-term application of adrenergic agonists modulates nociceptive ion channels

Dorsal root ganglia (DRG) neurons transduce and convey somatosensory information from the periphery to the central nervous system. Adrenergic mediators are known to modulate nociceptive inputs in DRG neurons, acting as up- or down-regulators of neuronal excitability. They are also important in the development of sympathetic neuropathy. ATP-activated P2X channels and capsaicin-activated TRPV1 channels are directly involved in the transduction of nociceptive stimuli. In this work, we show that long-term (up to 3 days) in vitro stimulation of DRG neurons with selective α1-adrenergic agonist increased slow but not fast ATP-activated currents, with no effect on capsaicin currents. Selective agonists for α2, β1 and β3-adrenergic receptors decreased capsaicin activated currents and had no effect on ATP currents. Capsaicin currents were associated with increased neuronal excitability, while none of the adrenergic modulators produced change in rheobase. These results demonstrate that chronic adrenergic activation modulates two nociceptive transducer molecules, increasing or decreasing channel current depending on the adrenergic receptor subtype. These observations aid our understanding of nociceptive or antinociceptive effects of adrenergic agonists.

Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats.

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014)μmol] > oxymetazoline [0.25 (0.22-0.28) μmol] > naphazoline [0.42 (0.34-0.53)μmol] = bupivacaine [0.43 (0.37-0.50) μmol] > xylometazoline [1.34 (1.25-1.45)μmol] > lidocaine [5.86 (5.11-6.72) μmol] > tetrahydrozoline [6.76 (6.21-7.36)μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75 ). Co-administration of lidocaine (ED50 ) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Surgical stress quickly affects the numbers of circulating B-cells and neutrophils in murine septic and aseptic models through a β2 adrenergic receptor

Sepsis is a pathology accompanied by increases in myeloid cells and decreases in lymphoid cells in circulation. In a murine sepsis model induced by cecum ligation and puncture (CLP), increasing numbers of neutrophils and decreasing levels of B-cells in circulation are among the earliest changes in the immune system. However, to date, the mechanisms for these changes remain to be elucidated. The study here sought to elucidate mechanisms underlying the changes in the leukocyte levels after CLP and also to determine what, if any, role for an involvement of the sympathetic nervous system (SNS). Here, male C57/BL6 mice were subjected to CLP or sham-CLP (abdominal wall incised, but cecum was not punctured). The changes in the number of circulating leukocytes over time were then investigated using flow cytometry. The results showed that a sham-CLP led to increased polymorphonuclear cells (PMN; most of which are neutrophils) and decreased B-cells in the circulation to an extent similar to that induced by CLP. Effects of adrenergic agonists and antagonists, as well as of adrenalectomy, were also examined in mice that underwent CLP or sham-CLP. Administering adrenaline or a β2 adrenergic receptor agonist (clenbuterol) to mice 3 h before sacrifice produced almost identical changes to as what was seen 2 h after performing a sham-CLP. In contrast, giving a β2 adrenergic receptor antagonist ICI118,551 1 h before a CLP or sham-CLP suppressed the expected changes 2 h after the operations. Noradrenaline and an α1 adrenergic receptor agonist phenylephrine did not exert significant effects. Adrenalectomy 24 h before a sham-CLP significantly abolished the expected sham-CLP-induced changes seen earlier. Clenbuterol increased splenocyte expression of Cxcr4 (a chemokine receptor gene); adrenalectomy abolished sham-CLP-induced Cxcr4 expression. A CXCR4 antagonist AMD3100 repressed the sham-CLP-induced changes. From these results, it may be concluded that sepsis-induced activation of the SNS may be one cause for immune dysfunction in sepsis – regardless of the pathogenetic processes.

Possible Regulation of P-glycoprotein Function by Adrenergic Agonists in a Vascular-luminal Perfused Preparation of Small Intestine

Although the functions of small intestine are largely regulated by enteric nervous system (ENS), an independent intrinsic innervation, as well as central nervous system (CNS), the neural regulation of drug absorption from the small intestine still remains to be clarified. To obtain some information on it, the effect of adrenergic agonists on P-glycoprotein (P-gp) function was investigated by utilizing a vascular-luminal perfused rat small intestine. Adrenaline significantly decreased the secretion of rhodamine-123 (R-123) into the intestinal lumen, but dibutyryl cAMP (DBcAMP) significantly enhanced R-123 secretion. The inhibition study with quinidine clearly indicated that the decrease in secretory clearance of R-123 by adrenaline or the increase by DBcAMP would be attributed to the decrease or increase in P-gp activity, respectively. Expression levels of P-gp in whole mucosal homogenates were not changed at all by any chemicals examined, but those on brush border membrane (BBM) of intestinal epithelial cells were significantly decreased or increased by adrenaline or DBcAMP, respectively. Furthermore, changes in P-gp activity caused by adrenergic agonists and DBcAMP were significantly correlated with changes in expression level of P-gp in BBM, suggesting that the trafficking of P-gp from cytosolic pool to BBM would be regulated by adrenergic agonists and DBcAMP.

Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice.

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the β-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic β-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of β-oxidation and autophagy in the liver.

Effects of Adrenergic Agonists and Antagonists on Cardiopulmonary Function During Normobaric Hypoxia in Rat.

Pulmonary edema (PE) is an issue widely noted in acute exposure to hypoxia as seen in high altitude climbers, yet the etiology of this is not defined. Previous studies in rats showed that both hypoxia and strong sympathetic activation may induce PE. As acute exposure to hypoxia is accompanied by sympathetic activation, we assume that this may impair pulmonary circulation and contribute to the development of hypoxic PE. The aim of the present study was to investigate the effects of adrenergic agonists and antagonists as models for overstimulation and suppression, respectively, of sympathetic activity on cardiovascular function and formation of PE in hypoxic rats. Norepinephrine or adrenergic blockers were infused to rats exposed to normobaric hypoxia with 10% O2 over time intervals up to 24 h. Normoxic and hypoxic controls received 0.9% NaCl infusion. We evaluated hemodynamic function and lung histology. A significant decrease of left ventricular systolic function was observed after 6 h of hypoxia. This effect was less pronounced with α-adrenergic blockade but was more severe with combined α-plus β-adrenergic blockade. Norepinephrine delayed the onset of hypoxic left ventricular depression but did not reduce its degree. Significant PE developed after 16 h of hypoxia. It regressed under α- but not with β-adrenergic blockade, and was aggravated by combining hypoxia with norepinephrine. Almost half of the animals exposed to hypoxia over 16–24 h suffered cardiorespiratory arrest during the experiment and presented with signs of acute right ventricular failure. They had significantly elevated serum catecholamine concentrations and significantly stronger PE than the others. Notably, most of them had received norepinephrine or combined adrenergic blockade. Mild changes in serum catecholamine concentrations indicated that hypoxic sympathoadrenergic activation was only weak. Hence, it was not sufficient to prevent left ventricular depression. However, the results show that α-adrenergic mechanisms contribute to the formation of hypoxic PE. Adrenergic blockade but also sympathetic overactivity may induce pulmonary congestion, PE and acute right ventricular failure indicating that a fine balance of sympathetic activation under hypoxic conditions is crucial. This has important implications for climbers to high altitude as well as for patients suffering from hypoxia.

Adrenergic Modulation of Excitation Propagation in Peripheral Synapses

A long history of studies of the effect of catecholamines on various physiological processes, a multidirectional and ambiguous interpretation of these effects, and a widespread use of adrenergic drugs in clinical practice raises a question of the mechanisms of action of these compounds on various functionally important elements of a living organism. The neuromuscular synapse plays a leading role in ensuring locomotor and respiratory functions, as well as in the posture maintenance. There is a number of conflicting reports on the multidirectional effects of adrenergic agonists on the muscle contraction, the release of acetylcholine from the motor nerve endings, and the state of the postsynaptic membrane of muscle fibers. The purpose of this review is to systematize the information concerning the effects of adrenergic compounds on different stages of the process of excitation propagation in peripheral synapses and to highlight recently revealed opportunities of the application of adrenergic compounds for the treatment of various diseases associated with neuromuscular pathology.

Leptin and HPA axis activity in diabetic rats: Effects of adrenergic agonists

Type I Diabetes (T1D) is associated with reduced leptin levels and increased stress axis activity marked by elevations in norepinephrine (NE) levels in the paraventricular nucleus (PVN) of the hypothalamus. We hypothesized that leptin suppresses stress axis activity in T1D through central and peripheral mechanisms. In the first experiment, adult male Sprague Dawley rats were implanted with a cannula in the PVN and randomly divided into a non-diabetic group treated with vehicle (n = 6) and a diabetic group treated with streptozotocin (n = 13). Food intake and water intake was measured for 14 days. On the last day, a subset of diabetic rats were treated with 500 µg of leptin i.p. Rats were subjected to push-pull perfusion of the PVN and hourly blood sampling for 5 h. In the next experiment, diabetic rats were treated either with an alpha-2 adrenergic agonist, clonidine (CLON), or a beta adrenergic agonist isoproterenol (ISO), to reverse the effects of leptin. Rats were subjected to push pull perfusion and hourly blood sampling. In experiment 1, T1D increased food intake, water intake, NE release in the PVN and circulating CS levels. Leptin treatment decreased NE release modestly but produced a robust reduction in corticosterone (CS) levels. In experiment 2, CLON but not ISO was able to reverse the effect of leptin on NE levels in the PVN, however, both agonists were capable of blocking leptin’s effects on circulating CS. These results suggest that in diabetic rats, the sensitivity of the hypothalamus to beta adrenergic agonists is altered, while the adrenals remain sensitive to both alpha and beta adrenergic agonists.

Leishmania donovani promastigote: Effect of Adrenergic Agonists and Antagonist on Growth and Lipophosphoglycan Synthesis

ABSTRACTBackground: Leishmania is the causative agent of a spectrum of diseases in human ranging in severity from self-healing cutaneous form to disfiguring mucocutaneous lesion to deadly visceral form of leishmaniasis. The treatment is still suffering from toxicity of the present drug regimen and the emergence of drug resistant leishmaniasis. Successful immunotherapy is yet to develop. It is beneficial to venture the parasite second messenger systems for the development of successful antileishmanial agents. The role of adrenergic receptor agonists and antagonist in the growth of L. donovani promastigotes and the synthesis of phosphorylated macromolecules were addressed in this report. Materials and Methods: The present work is entirely experimental. The effect of dibutyryl cAMP (db-cAMP), dibutyryl cGMP (db-cGMP), epinephrine, isoproterenol and propranolol on the growth of L. donovani promastigotes using defined medium were studied. Biosynthetically pulse labeling of promastigotes with [32P]-orthophosphate with or without experimental agents following SDS-PAGE and autoradiography was analyzed. Results: The growth of L. donovani promastigotes at 96 h culture was inhibited by 69%, 83, 52% and 95% with db-cAMP, epinephrine, isoproterenol and propranolol at 100 μM each, respectively in compared to control. Multiplication of parasite was stimulated by db-cGMP. The expression of lipophosphoglycan of the parasite was drastically affected in the following order with propranolol&gt;epinephrine&gt;cAMP&gt;isoproterenol at 100 μM of each agent for 6 h exposure to the promastigotes. Conclusion: The growth of the parasite and the synthesis of lipophosphoglycan were significantly more inhibited by epinephrine or propranolol in a dose dependent manner than cAMP or isoproterenol.Keywords: cAMP; cGMP; epinephrine; Leishmania donovani; LPG; propronolol.

Altered pharmacological effects of adrenergic agonists during hypothermia.

Rewarming from accidental hypothermia is often complicated by hypothermia-induced cardiac dysfunction, calling for immediate pharmacologic intervention. Studies show that although cardiac pharmacologic support is applied when rewarming these patients, a lack of updated treatment recommendations exist. Mainly due to lack of clinical and experimental data, neither of the international guidelines includes information about pharmacologic cardiac support at temperatures below 30 °C. However, core temperature of accidental hypothermia patients is often reduced below 30 °C. Few human studies exploring effects of adrenergic drugs during hypothermia have been published, and therefore prevailing information is collected from pre-clinical studies. The most prominent finding in these studies is an apparent depressive effect of adrenaline on cardiac function when used in doses which elevate cardiac output during normothermia. Also noradrenaline and isoprenaline largely lacked positive cardiac effects during hypothermia, while dopamine is a more promising drug for supporting cardiac function during rewarming. Data and information from these studies are in support of the prevailing notion; not to use adrenergic drugs at core temperatures below 30 °C.

Effect of adrenergic agonists on coronary blood flow: a laboratory study in healthy volunteers.

Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α‐adrenergic receptors and β‐adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat‐free mass and were infused slowly to achieve steady‐state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat‐by‐beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD. Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low‐dose, steady‐state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β‐adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat‐by‐beat imaging methodologies can be used in future studies to evaluate age‐, sex‐, and disease‐ differences in adrenergic control of coronary blood flow.

Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine.

RationaleSpatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by noradrenaline (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for cognitive enhancers of spatial working memory. Of the three classes of NA receptor potentially involved, the α2 and α1 classes seem most significant, though agents targeting these receptors have yielded mixed results. This may be partially due to the use of behavioural assays that do not translate effectively from the laboratory to the clinical setting. Use of a paradigm with improved translational potential may be essential to resolve these discrepancies.ObjectivesThe objective of this study was to assess the effects of PFC-infused α2 and α1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trial-unique non-matching to location (cTUNL) task in rats.MethodsYoung male rats were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of GABA agonists for task validation, and phenylephrine and guanfacine to determine the effects of adrenergic agonists on task performance.ResultsInfusion of muscimol and baclofen resulted in a delay-dependent impairment. Administration of the α2 agonist guanfacine had no effect, whilst infusion of the α1 agonist phenylephrine significantly improved working memory performance.ConclusionsSpatial working memory as measured in the rat cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the α1 receptor in this facilitation.

Ephedrine and propofol for induction of general anesthesia can decrease intraoperative hypothermia in patients undergoing plastic and breast surgery: a randomized, controlled trial

Background: Ephedrine has vasoconstrictive and mild ?-adrenergic agonist effects that may be able to decrease intraoperative core temperature hypothermia. However, its efficacy is still unclear. Objectives: To determine the efficacy of ephedrine given during induction to maintain core temperature during plastic and breast surgery under general anesthesia. Materials and Methods: A prospective, randomized, double-blinded study was approved by our Institutional Review Board and registered with the Thai Clinical Trials Registry as TCTR20141212002. We randomly assigned 30 patients to receive mixture of propofol and ephedrine (ephedrine group, n = 15) or a mixture of propofol and normal saline (control group, n = 15) for induction of general anesthesia. The tympanic temperature (core temperature before intubation), esophageal temperature (core temperature after intubation), index temperature (peripheral temperature), systolic and diastolic blood pressure were compared between groups and baselines. Results: During surgery, patients in ephedrine group showed better esophageal temperature maintenance than those in the control group. Whereas systolic blood pressure in ephedrine group was significantly higher than in the control group in early phase after induction. Conclusions: A bolus dose of ephedrine given during induction can decrease core temperature loss during plastic and breast surgery under general anesthesia. Keywords: Ephedrine, general anesthesia, hypothermia, temperature

Extracorporeal transient distal penile corporoglanular shunt in early ischemic priapism treatment.

Ischemic priapism, which is a compartment syndrome, needs urgent treatment in order to nourish corpora cavernosa. As the first step, the aspiration of blood and/or the irrigation of the cavernosal bodies are performed to prevent fibrotic activity and secure erectile capability. While performing aspiration and irrigation, there are some risks of the procedure in which most refrained one is cardiovascular side effects of adrenergic agonists. We aimed to evaluate extracorporeal transient distal penile corporoglanular shunt technique in place of aspiration/ irrigation techniques for early ischemic priapism treatment. In this transient shunt technique, a sterile closed system blood collection set (BD Vacutainer, Cat. No.: 367282; NJ, USA), which has two 21G needles, was used. The length of the needle and tubing was 19 mm. (0.75 inch) and 178 mm. (7 inches), respectively. This blood collection set was designed to be used not only for blood collection but can also be used for short term infusions (maximum 2 hours). Ten patients out of fifteen with early ischemic priapism were successfully treated with this transient shunt technique. The permanent detumescence achieved in the first 10 minutes in nine out of fifteen patients.No additional procedure needed after the disappearance of rigidity in successfully treated patients. The permanent detumescence achieved in the first 10 minutes in nine out of fifteen patients. We demonstrated that this extracorporeal transient shunt technique gets some advantages over aspiration and irrigation in early ischemic priapism treatment. Our results indicate thatthe presented technique to be offered for the patients with an ischemic priapism episode of no more than 7 hours.

Frequency of coprescription and potential risk of bronchospasm in Colombian patients users of topical antiglaucomatous betablockers and bronchodilators

Background: Cardiovascular and respiratory effects of adrenergic agonists used in diseases like chronic obstructive pulmonary disease (COPD), and β-blockers used in glaucoma generate competitive antagonism on the same adrenergic receptor when used simultaneously with the aggravation that the β-blockers can precipitate bronchospasm. Objective: Determine de frequency of coprescription and potential risk of interaction between bronchodilators and topical antiglaucomatous β-blockers for glaucoma in a database of Colombian patients. Methods: Cross-sectional study in patients older than 40 years treated for bronchial disorders and glaucoma between January 1 and October 31, 2012. We used information about 6.2 million population database of individuals enrolled in Health System of Colombia. In the database it was assessed all prescription records of topical β-blockers and any bronchodilators and the frequency of potential risk of developing drug-induced bronchospasm. The identified patients were informed to the physician responsible to the health attention. Results: We found 1756 patients were receiving topical β-blockers and bronchodilators. Most were women (63.2 %), mean age 73.3 ± 11.1 years, in 61 cities. The antiglaucoma drugs more employees were: timolol (67.5 % of patients), timolol/dorzolamide (18.8 % of patients) and bronchodilators: salbutamol (43.8 % of patients) and ipratropium (41.8 % of patients). The more frequent risk associations of bronchospasm were: salbutamol + timolol (n = 890, 50.6 % of patients), ipratropium bromide + timolol (n = 827, 47.1 %) salbutamol + timolol + dorzolamide (n = 258, 14.6 % of patients) and ipratropium bromide + timolol + dorzolamide (n = 255, 14.5 % of patients). Conclusions: The database research of Negative Outcomes Associated with Medication is useful to know problems in prescription of many therapies. There are potential interactions between antiglaucoma drugs and bronchodilators that increase the risk of precipitating bronchospasm in patients who present asthma, COPD and glaucoma in Colombia. Implementing strategies that link drug dispensers and medical insurers can reduce risks associated with the medication.

Umeclidinium–vilanterol: First once-daily dual bronchodilator for COPD

Umeclidinium–vilanterol: First once-daily dual bronchodilator for COPD

Transient Distal Penile Corporoglanular Shunt as an Adjunct to Aspiration and Irrigation Procedures in the Treatment of Early Ischemic Priapism

PurposeIschemic priapism, a compartment syndrome, requires urgent treatment in order to nourish the corpora cavernosa. As the first step, aspiration of blood and irrigation of the cavernosal bodies is performed to prevent fibrotic activity and secure erectile capability. During aspiration, there are risks of cardiovascular side effects of adrenergic agonists. We aimed to evaluate a transient distal penile corporoglanular shunt technique in place of aspiration and irrigation techniques for treatment of early ischemic priapism.Materials and MethodsA transient distal penile shunt was applied to 15 patients with early ischemic priapism between January 2011 and May 2012. Priapism duration, history, causes, pain, and any prior management of priapism were assessed in all patients. A complete blood count and penile Doppler ultrasonography were performed, which showed attenuated blood flow in the cavernosal artery. A sterile closed system blood collection set, which has two needles and tubing, was used for the transient distal penile shunt.ResultsTen of 15 patients with early ischemic priapism were successfully treated with this transient shunt technique. No additional procedures were needed after the resolution of rigidity in the 10 successfully treated patients.ConclusionsThe transient nature of this technique is an advantage over aspiration and irrigation in the treatment of early ischemic priapism. Our results indicate that the technique can be offered for patients with an ischemic priapism episode of no more than 7 hours.

G015 Adrenergic regulation of the resting membrane potential in the left atrium and thoracic veins of the rat

The physiology of cardiac muscle in thoracic veins is of interest as a source of ectopic activity which can lead to paroxystic atrial fibrillation (Haissaguerre et al. 1998 N Engl J Med 339: 659-666 ; Chen et al. 1999 Circulation 100:1879-1886). We have shown that noradrenalin can induce automatic ectopic activity in the pulmonary vein of the rat (Maupoil et al. 2007 Br J Pharmacol 150:899-905). Here we describe the effects of adrenergic agonists upon the resting membrane potential recorded with intracellular microelectrodes from cardiac muscle in the left atrium (LA), pulmonary veins (PV) and superior vena cava (SVC) of the rat. Isolated tissues were continuously perfused with Krebs-Heinseleit solution aerated with 95 % O2, 5 % CO2 and maintained at 36-37 °C. The quiescent resting membrane potentials were: LA −84±1 mV (n=14), SVC −74±1 mV (n=14), PV −69±1 mV (n=17). In each tissue noradrenalin (10-5M) induced a biphasic response with an initial hyperpolarisation (LA −3±1 mV, SVC −9±1 mV, PV −8±1 mV) followed by a depolarisation (LA +1±2 mV, SVC +15±2 mV, PV +34±1 mV). Only in PV did noradrenalin induce automatic electrical activity when the membrane potential reached ∼−50 mV. The α-adrenergic agonist cirazoline (10-6M) induced a monophasic depolarisation of the resting membrane potential in each tissue: to −80±2 mV in LA, to −49±1 mV in SVC and to −34±1 mV in PV. In no case did cirazoline induce automatic electrical activity. The β-adrenergic agonist isoprenaline (10-7M) induced a monophasic hyperpolarisation of the resting membrane potential in each tissue: to −87±1 mV in LA, to −79±2 mV in SVC and to −80±2 mV in PV. 1. There are significant differences between the resting membrane potentials of the left atrium and both thoracic veins. 2. The responses of the resting membrane potential to adrenergic stimulation are qualitatively similar but quantitatively different with LA < SVC < PV. 3. Depolarisation is not sufficient to induce automatic electrical activity.

Effects of adrenergic agonists on the extrahepatic expression of vitellogenin Ao1 in heart and brain of the Chinese rare minnow ( Gobiocypris rarus)

Teleost vitellogenins (VTGs) are large multidomain apolipoproteins and traditionally considered as the estrogen responsive precursors of the major egg yolk proteins. We identified five clones encoding VTGs, about 16% of the random EST clones from our constructed cDNA library from Chinese rare minnow liver tissue treated with 17β-estradiol (E2). Full-length vtgAo1 has been obtained based on the sequence information of four partial cDNA inserts by RACE. The inducibility of the vtgAo1 expression in liver by E2 was confirmed by RT-PCR. The presence of vtgAo1 transcripts have been observed primarily in liver. However, a significant level of the vtgAo1 was found in an unexpected location, heart, particularly in atrial cells by RT-PCR and whole mount in situ hybridization analyses. The vtgAo1 mRNA expression in heart and liver tissue could be suppressed by both α-adrenergic agonist, phenylephrine (PE) and β-adrenergic agonist, isoproterenol (ISO). The expression of VTG in the heart observed in the present studies suggested it may provide protection from surplus intracellular lipids in fish cardiomyocytes as triglyceride transport proteins do in mammals. The results also indicated that the production of teleost vtg in vivo can be regulated by not only estrogenic agents, but adrenergic signals as well.

The role of adrenergic agonists on glycogenolysis in rat hepatocyte cultures and possible involvement of NO

Certain liver metabolic diseases point to the presence of disturbances in glycogen deposition. Epinephrine raises the cAMP level that activates protein kinase A leading to the activation of phosphorylase and glycogen breakdown. In the present report, we sought to investigate whether NO is produced during adrenoceptor agonist-induced glycogenolysis in rat hepatocytes in cultures. Isolated glycogen rich rat hepatocytes in cultures were used. NO production (NO(2)(-)) was assessed under the effect of adrenergic agonists and adrenergic agonist/antagonist pairs, dibutyryl cyclic AMP sodium-potassium salt (db-cAMP), NO synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). The inducible NO synthase (iNOS) mRNA was examined by the reverse transcription-polymerase chain reaction (RT-PCR). Glycogenolysis was quantified by glucose levels released into medium. The amount of glucose and NO(2)(-) released by hepatocytes was increased as a result of epinephrine, phenylephrine or db-cAMP treatments. The increase in glucose and NO(2)(-) released by epinephrine or phenylephrine was blocked or reduced by prazosin pretreatment and by NOS inhibitors aminoguanidine and L-NAME. iNOS gene expression was up-regulated by epinephrine. It can be concluded that glycogenolysis occurs through -adrenoceptor stimulation and a signaling cascade may involve NO production.