Beta-adrenoceptor Blockade Research Articles

Beta-adrenergic receptor blockade and prostate peptide growth factor expression in the rat

Background and aim: In the rat prostate, beta-adrenoreceptor (β-AR) stimulation does not alter basal prostatic tone but may inhibit α1-AR-mediated, field stimulation-induced or receptor-independent contractile responses. The present study was designed to assess the alteration of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGFβ) expression in the rat ventral prostate in response to β-AR blockade with propranolol.Results: At sacrifice, body weight as well as ventral prostate weight and prostate morphology were not significantly affected by propranolol treatment. Stromal elements and the majority of prostatic epithelial cells in control animals demonstrated positive staining for the anti-bFGF antibody, while positive staining for TGFβ was seen only in epithelial cells. Propranolol treatment resulted in considerable decrease of bFGF staining intensity in both stromal and epithelial cells, while the immunostaining pattern for TGFβ was almost abolished.Results and Conclusions: The results from this study provide evidence to suggest that prolonged propranolol treatment affects peptide growth expression in the rat ventral prostate as in other tissues, and confirms the notion that autonomic nervous system controls, at least partly, prostate gland functional characteristics. Moreover, it may also affect prostate homeostasis by intervening in stromal-epithelial interaction through alterations in the expression of peptide growth factors without affecting prostate volume.

Simultaneous blockade of alpha and beta adrenoceptors impairs cutaneous wound healing in rats

Recent studies showed that propranolol administration (beta-antagonist), but not phentolamine administration (alpha-antagonist), delays cutaneous wound healing. However, alpha adrenoceptor activation may be participating in propranolol-induced alterations. This study aims to investigate the effects of simultaneous blockade of beta and alpha adrenoceptors on cutaneous wound healing. Rats were treated with propranolol plus phentolamine dissolved in water. An excisional lesion was done and measured. Lesions were formalin-fixed and paraffin-embedded 21 days after wounding. Sections were stained with haematoxylin and eosin, toluidine blue and Sirius red, and immunostained for alpha-smooth muscle actin or proliferating cell nuclear antigen. Administration of propranolol plus phentolamine reduced wound contraction and re-epithelialization, but increased cellular proliferation and the number of mast cells. There was no difference in myofibroblast density, collagen fibre organization and polymorphonuclear number between the control and treated groups. Simultaneous blockade of beta and alpha adrenoceptors impairs cutaneous wound healing. Furthermore, propranolol-induced impairment on cutaneous wound healing does not occur through alpha adrenoceptor activation.

Hypotensive Medication, Statins, and the Risk of Glaucoma

PURPOSE. To examine whether treatment with oral blood-pressure-lowering medication or statins influences the risk of glaucoma. METHODS. This study was a case-control investigation, nested within a computerized primary care database of 177 general practices across the United Kingdom; 8778 cases diagnosed and/or treated for glaucoma between 2000 and 2007, and 8778 glaucoma-free controls matched for age, sex, and practice. Odds ratios for treatment with oral antihypertensives (including selective beta(1) and nonselective beta-blockers) and statins in the 5 years before diagnosis were calculated by logistic regression, adjusted for a marker of socioeconomic position and number of drug types prescribed (as a measure of health service usage). RESULTS. Prevalence of oral beta-blocker use in the 5 years before diagnosis was lower in the cases (22.5%) than in the controls (23.6%), adjusted odds ratio (OR) 0.87 (95% confidence interval [CI], 0.80-0.94). This effect was presence with treatment with beta(1)-selective medications (OR, 0.81; 95% CI, 0.74-0.88) but not with nonselective medications (OR, 1.08; 95% CI, 0.94-1.24). The prevalence of thiazide use was higher among the glaucoma cases than among the controls (OR, 1.13; 95% CI, 1.04-1.23). Neither statins nor other antihypertensive treatments were associated with the risk of glaucoma. CONCLUSIONS. Oral beta(1) beta-blockers may protect against development of glaucoma. The current consensus on the relative importance of beta(2) receptor blockade in treating glaucoma may have to be reviewed. Changes in prescribing oral beta-blockers for cardiovascular disorders may affect the number of those who eventually have glaucoma. There is no evidence to suggest that statins have a preventive role in glaucoma.

Effects of physical training on aerobic capacity in frail elderly people (75+ years). Influence of lung capacity, cardiovascular disease and medical drug treatment: a randomized controlled pilot trial

Frail elderly people often suffer from a combination of unintentional weight loss and/or low body mass index, as well as a low physical activity level. No studies have investigated the effect of physical training alone or in combination with nutritional intervention on aerobic capacity in frail elderly people. The aim of this pilot study was to determine if a physical training program can affect aerobic capacity in frail elderly people. Ninety-six community-dwelling frail elderly people (58 women) were included in the study. Subjects were randomized to four different groups: i) physical training program (aerobic, muscle strength, balance), ii) a nutritional intervention program (individually targeted advice and group sessions), iii) a combination of these interventions, and iv) a control group. At baseline, subjects were screened for aerobic capacity, leg muscle strength, spirometry, heart disease and cardiovascular drugs. Aerobic capacity and leg muscle strength were analyzed immediately after the 3-month intervention period (1st follow-up), and after another 6 months (2nd follow-up). Subjects mean age was 83 years. The mean compliance rate with the physical training program was 65%. There were no observed effects on aerobic capacity measured as maximal workload, or work time, with or without beta-receptor blockade. Subjects in the training groups without lung disease significantly increased maximal work time when compared with subjects with lung disease. Physical training significantly increased lower extremity muscle strength compared with nutrition alone at the 1st follow-up. No serious adverse events occurred during assessment or physical training. Further studies with larger sample sizes and a more specific aerobic component in the training program are necessary before any further conclusions can be drawn.

Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3

AimsClinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). β-Adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease.Methods and resultsWe studied effects of autonomic modulation on arrhythmias in vivo and in vitro and quantified sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (ΔKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice). Cholinergic stimulation by carbachol provoked bigemini and TdP in freely roaming LQT3 mice. No arrhythmias were provoked by physical stress, mental stress, isoproterenol, or atropine. In isolated, beating hearts, carbachol did not prolong action potentials per se, but caused bradycardia and rate-dependent action potential prolongation. The muscarinic inhibitor AFDX116 prevented effects of carbachol on heart rate and arrhythmias. β-Adrenoceptor stimulation suppressed arrhythmias, shortened rate-corrected action potential duration, increased rate, and minimized difference in late sodium current between genotypes. β-Adrenoceptor density was reduced in LQT3 hearts. Acute β-adrenoceptor blockade by esmolol, propranolol or chronic propranolol in vivo did not suppress arrhythmias. Chronic flecainide pre-treatment prevented arrhythmias (all P < 0.05).ConclusionCholinergic stimulation provokes arrhythmias in this model of LQT3 by triggering bradycardia. β-Adrenoceptor density is reduced, and β-adrenoceptor blockade does not prevent arrhythmias. Sodium channel blockade and β-adrenoceptor stimulation suppress arrhythmias by shortening repolarization and minimizing difference in late sodium current.

Beta-adrenergic receptor blockade and prostate peptide growth factor expression in the rat

In the rat prostate, beta-adrenoreceptor (beta-AR) stimulation does not alter basal prostatic tone but may inhibit alpha1-AR-mediated, field stimulation-induced or receptor-independent contractile responses. The present study was designed to assess the alteration of basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGFbeta) expression in the rat ventral prostate in response to beta-AR blockade with propranolol. At sacrifice, body weight as well as ventral prostate weight and prostate morphology were not significantly affected by propranolol treatment. Stromal elements and the majority of prostatic epithelial cells in control animals demonstrated positive staining for the anti-bFGF antibody, while positive staining for TGFbeta was seen only in epithelial cells. Propranolol treatment resulted in considerable decrease of bFGF staining intensity in both stromal and epithelial cells, while the immunostaining pattern for TGFbeta was almost abolished. The results from this study provide evidence to suggest that prolonged propranolol treatment affects peptide growth expression in the rat ventral prostate as in other tissues, and confirms the notion that autonomic nervous system controls, at least partly, prostate gland functional characteristics. Moreover, it may also affect prostate homeostasis by intervening in stromal-epithelial interaction through alterations in the expression of peptide growth factors without affecting prostate volume.

Recommendations for advancing the care of Canadians living with refractory angina pectoris: A Canadian Cardiovascular Society position statement

Refractory angina (RFA) is a debilitating disease characterized by severe, unremitting cardiac pain (1,2). This pain or discomfort, by definition, is resistant to all conventional treatments for coronary artery disease (CAD) including nitrates, calcium channel and beta-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions and coronary artery bypass grafting (1,2). Patients living with RFA have a low annual mortality rate of 3% but suffer from a severely impaired health-related quality of life (3). They typically experience recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, activity restriction and inability to self-manage (4–7). As more patients survive primary and subsequent cardiac events, the global prevalence of RFA is ever increasing (1,2,8,9).

Changes in pulmonary blood flow distribution in monocrotaline compared with hypoxia-induced models of pulmonary hypertension: assessed using synchrotron radiation

We have previously described anatomical changes in pulmonary blood flow distribution in chronic hypoxic rats, associated with pulmonary arterial hypertension (PAH). In this study, we utilized synchrotron radiation microangiography to compare these changes in pulmonary blood flow with a PAH-model induced with monocrotaline (MCT), as the etiology for these two models of PAH is different. Three weeks after a subcutaneous injection of MCT (60 mg/kg) or vehicle (control), Sprague-Dawley rats were anesthetized, and microangiography was performed on the left lung to assess branching distribution of pulmonary blood flow and changes in vessel diameter during acute (8% O2 for 4 min) hypoxic pulmonary vasoconstriction--before and after sympathetic beta-adrenoceptor blockade (propranolol, 2 mg/kg, intravenous). Comparisons were made with chronic hypoxic rats using data previously published. We observed that adverse changes in pulmonary blood flow were comparable for both chronic hypoxia and MCT models of PAH. Specifically, the number of opaque third and fourth generation vessels was significantly and equally fewer than that of control rats. The acute hypoxic pulmonary vasoconstriction was not altered in the hypertensive lung, though sympathetic modulation of pulmonary vasoreactivity was enhanced by chronic hypoxia, but not MCT. In summary, we have demonstrated comparable adverse changes in pulmonary blood flow for chronic hypoxia and MCT models of PAH. In contrast, modulation of the hypoxic pulmonary vasoconstriction differs between the two PAH models, likely due to the impact that different pathological pathways have on the physiology of the whole organism. Such differences between models of PAH should be considered in future studies.

Adrenaline but not noradrenaline is a determinant of exercise‐induced lipid mobilization in human subcutaneous adipose tissue

The relative contribution of noradrenaline (norepinephrine) and adrenaline (epinephrine) in the control of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise was evaluated in men treated with a somatostatin analogue, octreotide. Eight lean and eight obese young men matched for age and physical fitness performed 60 min exercise bouts at 50% of their maximal oxygen consumption on two occasions: (1) during i.v. infusion of octreotide, and (2) during placebo infusion. Lipolysis and local blood flow changes in SCAT were evaluated using in situ microdialysis. Infusion of octreotide suppressed plasma insulin and growth hormone levels at rest and during exercise. It blocked the exercise-induced increase in plasma adrenaline while that of noradrenaline was unchanged. Plasma natriuretic peptides (NPs) level was higher at rest and during exercise under octreotide infusion in lean men. Under placebo, no difference was found in the exercise-induced increase in glycerol between the probe perfused with Ringer solution alone and that with phentolamine (an alpha-adrenergic receptor antagonist) in lean subjects while a greater increase in glycerol was observed in the obese subjects. Under placebo, propranolol infusion in the probe containing phentolamine reduced by about 45% exercise-induced glycerol release; this effect was fully suppressed under octreotide infusion while noradrenaline was still elevated and exercise-induced lipid mobilization maintained in both lean and obese individuals. In conclusion, blockade of beta-adrenergic receptors during exercise performed during infusion of octreotide (blocking the exercise-induced rise in adrenaline but not that of noradrenaline) does not alter the exercise-induced lipolysis. This suggests that adrenaline is the main adrenergic agent contributing to exercise-induced lipolysis in SCAT. Moreover, it is the combined action of insulin suppression and NPs release which explains the lipolytic response which remains under octreotide after full local blockade of fat cell adrenergic receptors. For the moment, it is unknown if results apply specifically to SCAT and exercise only or if conclusions could be extended to all forms of lipolysis in humans.

LANDIOLOL, AN ULTRASHORT-ACTING β1-ADRENOCEPTOR ANTAGONIST, HAS PROTECTIVE EFFECTS IN AN LPS-INDUCED SYSTEMIC INFLAMMATION MODEL

Previous studies suggest that the blockade of beta-adrenoceptors augments the release of inflammatory regulators in response to proinflammatory stimuli. High-mobility group box 1 (HMGB-1) is a key mediator in the development of sepsis. We investigated whether landiolol, a short-acting selective beta1-adrenoceptor-blocking agent, can attenuate acute lung injury and cardiac dysfunction in a rat model of endotoxin-induced sepsis. We administered LPS i.v. to rats, with or without simultaneous treatment with landiolol (0.1 mg/kg per min). After the induction of sepsis by LPS treatment, we measured cytokine and HMGB-1 levels in the serum and lung tissue. In addition, we performed histopathology, determined wet-to-dry weight ratios, and measured cardiac function and cell signaling in the lung. Cotreatment with landiolol was associated with significantly less severe disease, as assessed by lung histopathology and cardiac function metrics. Serum and lung HMGB-1 levels were lower over time among landiolol-treated animals. Furthermore, nuclear factor-kappaB activity was inhibited by the administration of landiolol. Cotreatment with the selective beta1-adrenoceptor-blocking agent landiolol protects against acute lung injury and cardiac dysfunction in a rat model of LPS-induced systemic inflammation. Treatment was associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage.

Propranolol treatment affects ventral prostate blood vessels and serum testosterone concentrations in adult rats.

The influence of prolonged beta-adrenergic receptor blockade on stereologic parameters of the ventral prostate and serum testosterone concentrations was examined in adult rats injected with propranolol (0.1 or 0.4 mg kg-1/day) for 15 or 30 consecutive days. Both doses of propranolol reduced the relative and absolute volume of the ventral prostate blood vessels. This effect was prevented by simultaneous administration of urapidil, an alpha 1-adrenergic receptor antagonist, indicating that a compensatory vasoconstriction took place as a consequence of propranolol treatment. Serum testosterone concentration was significantly increased following the 30-day application of the lower dose of the drug. These results show that prolonged administration of propranolol, although not affecting the epithelial component of the gland, may indirectly influence prostatic function by reducing the blood flow to the gland.

Beta‐adrenoceptor blockade delays granulation tissue formation in polyurethane sponge implants

The role of adrenoceptors in granulation tissue formation is not well understood. The aim of this study was to investigate the effects of alpha- and beta-adrenoceptor blockade on granulation tissue development using polyurethane (PU) implants in the rat. Animals were treated orally with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist) or phentolamine (alpha1- and alpha2-antagonist) until euthanasia. The control group received only water. All animals received subcutaneous implants of PU sponges. After 14 days, implants were collected, formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin and Sirius red and immunostained for CD68 and alpha-smooth muscle actin. The number of inflammatory cells and the volume density of myofibroblasts and blood vessels were lower in the control group than in the propranolol- and atenolol-treated groups. The collagen fiber score was greater in the control group than in the propranolol- and atenolol-treated groups. The inflammatory infiltrate, collagen fiber score, blood vessel density or myofibroblast differentiation was not affected by phentolamine. The percentage of fibrovascular invasion was greater in the antagonist-treated groups than in the control group. Blockade of beta1- and beta2-adrenoceptors, but not alpha-adrenoceptors, impairs granulation tissue development in PU implants due to interference with the inflammatory response.

Differential involvement of cholinergic and beta-adrenergic systems during acquisition, consolidation, and retrieval of long-term memory of social and neutral odors

Acetylcholine and norepinephrine have been implicated during different kinds of social recognition that involves olfactory memory formation. For example, blockade of muscarinic and beta-adrenergic receptors has been shown to impair short-term memory of both socially relevant as well as of neutral odors. However, previous studies have not explicitly compared the role of cholinergic and adrenergic modulation in long-term memory for socially relevant odor vs. incidental odor stimuli. In this work, we studied the function of muscarinic and beta-adrenergic receptors during acquisition and/or consolidation of a novel odor and during the retrieval of a familiar odor. The effects of systemic injections of scopolamine and propranolol, before and after presentation of estrous urine odor or mint odor, were evaluated by a long-term odor habituation task. The results demonstrated that scopolamine disrupts memory acquisition and/or consolidation of mint odor, and did not have any effect during retrieval of mint odor memory. Conversely, scopolamine disrupts memory consolidation and retrieval of estrous odor, depending on the dose applied. Propranolol injections have no effect on acquisition or consolidation for mint or estrous odor, but disrupt memory retrieval of familiar odor regarding their social/sexual or neutral content. These results demonstrate that muscarinic receptors are required differentially during long-term odor memory formation and for familiar odor recognition depending on the socially relevant content of the stimulus. Furthermore, the beta-adrenergic system could play an important role in memory recognition for familiar odors, regardless of the sexual/social or neutral content of the stimuli.

β‐1 and β‐2, but not α‐1 and α‐2, adrenoceptor blockade delays rat cutaneous wound healing

The sympathetic nervous system plays an important role in wound healing, but its mechanism of action is poorly understood. The aim of this study was to investigate the effects of beta- and alpha-adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist), or phentolamine (alpha1- and alpha2-antagonist) dissolved in drinking water. A full-thickness excisional lesion was created and the wound area was measured. Fourteen days after wounding, lesions and adjacent skin were removed, formalin-fixed, and paraffin-embedded. Sections were stained with hematoxylin-eosin and toluidine blue, and immunostained for alpha-smooth muscle actin and proliferating cell nuclear antigen. Wound contraction was delayed in propranolol- and atenolol-treated animals but not in phentolamine-treated animals. Reepithelialization was decreased only in propranolol-treated animals. beta1- and beta2-adrenoceptor blockade delayed leukocyte migration, epidermal and connective tissue cell proliferation, myofibroblastic differentiation, and mast cell migration. The volume density of blood vessels was increased in the propranolol- and atenolol-treated animals compared with controls. The levels of matrix metalloproteases (MMP-2 and MMP-9) decreased in the propranolol- and atenolol-treated animals. alpha1- and alpha2-adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro-MMP-9 levels. In conclusion, beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays cutaneous wound healing.

β 2 Adrenoreceptor blockade attenuates the hyperinflammatory response induced by traumatic injury

Major operative injury initiates immunologic changes that may result in a systemic inflammatory response, leading to organ dysfunction/sepsis. Catecholamines seem to be key mediators. The effects of beta(2) receptor blockade in vitro and in vivo before and after operative injury were studied to clarify their role. In vitro studies were done in RAW 264.7 cells using epinephrine (50 micromol/L) with or without alpha(2)- and beta(2)-receptor blockade. Comparative gene expression analysis on the Toll-like receptor (TLR)-4 receptor signaling pathway was performed between RAW cells pretreated with epinephrine with subsequent lipopolysaccharide (LPS) stimulation versus LPS alone. Confirmatory studies were performed by real-time reverse transcription polymerase chain reaction (RT-PCR). Tumor necrosis factor (TNF)-alpha gene and protein expression were determined via real time RT-PCR and enzyme-linked immunosorbent assay, respectively. In vivo, Balb/C mice received no treatment nor injury (group I). Group II received operative injury and vehicle injection, group III received ICI 118,551 (beta(2)-receptor antagonist) 30 minutes before or in separate studies after operative injury. At 7 days, splenic macrophages were harvested and cytokine production was measured with or without LPS. In separate experiments, cecal ligation and puncture (CLP) was done 7 days after operation and survival determined. In vitro studies demonstrated that epinephrine pretreatment significantly increased TNF-alpha production with LPS stimulation (P < .05). beta(2)-Receptor blockade significantly attenuated (P < .05) LPS stimulated TNF-alpha production. MD-2, an essential coactivator of TLR-4 signaling, gene expression was significantly elevated when cells were pretreated with epinephrine before LPS exposure (P < .001). In vivo studies demonstrated a significant decrease (P < .05) in TNF-alpha and interleukin-6 production in the ICI 118,551 group. Similar findings were demonstrated measuring monocyte chemoattractant protein-1 and interferon-gamma cytokine levels (P < .05) versus no treatment. ICI 118,551 treatment 30 minutes before operation demonstrated a 31% reduction in mortality after CLP (P < .05). This study demonstrates that beta(2)-receptor blockade reduces macrophage cytokine production and improves survival showing the critical importance of catecholamines to the immunologic response in surgery.

Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation. Isolated rat hearts were randomized into three groups (n=8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5)M). Amitriptyline (5.5 x 10(-5)M) infusion following pretreatment with 5% dextrose or 10(-4)M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2)M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4)M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol+DPCPX group (168.8+/-4.9%, p<0.05; 170.8+/-6.9%, p<0.01; 174.0+/-6.9%, p<0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5+/-6.1%, p<0.05) compared to DPCPX pretreatment group. DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.

New perspectives on beta-adrenergic mediation of innate and learned fear responses to predator odor.

In the present study, we investigated the role of noradrenergic transmission in unconditioned and conditioned responses to predatory threats. First, we examined the effects of systemically injected beta-blockers on unconditioned and contextual conditioned response to cat odor. The centrally acting beta-blocker (propranolol) was able to impair unconditioned responses, as well as the acquisition of the contextual fear to cat odor; however, the peripherally acting (nadolol) was not effective. Next, we examined the neural substrate underlying the noradrenergic modulation of the defensive response to cat odor and focused on the dorsal premammillary nucleus (PMd), because it represents the hypothalamic site most responsive to predatory threats and, at the same time, presents a dense plexus of noradrenergic fibers. We were able to see that propranolol significantly reduced PMd-Fos expression in response to cat odor and that beta-adrenoceptor blockade in the PMd, before cat odor exposure, reduced defensive responses to the cat odor and to the cat odor-related environment. We have also shown that beta-adrenoceptor blockade in the PMd, before the exposure to cat odor-related context, impaired the contextual conditioned responses. Overall, the present results provide convincing evidence suggesting that central noradrenergic mediation is critical for the expression of unconditioned and contextual conditioned antipredatory responses. We have further shown that the PMd appears to be an important locus to mediate these beta-adrenoceptor effects.

Influence of atenolol on coronary artery spasm after acute myocardial infarction in a Japanese population

BackgroundJapanese patients with acute myocardial infarction (MI) have a greater incidence of coronary artery spasm than Caucasians. Some beta-blockers have been reported to aggravate coronary spasm. This study sought to assess the effects of beta-adrenoceptor blockade on coronary vasospasm in Japanese patients with acute MI who had been treated with primary angioplasty. MethodsIn 69 patients we analyzed the effect of atenolol 50 mg/day initiated the day after emergency primary angioplasty on the results of intracoronary ergonovine provocation test performed 4 weeks after onset. ResultsAmong 35 patients in the atenolol group, the drug was discontinued in 9 (26%) due to hemodynamic compromise. The remaining 26 in the atenolol group and 34 in the control group underwent the spasm provocation test. Atenolol did not significantly increase the incidence of coronary vasospasm (31% vs. 15% in the atenolol and control groups, respectively, p= 0.135). Multivariate analysis revealed that only the pre-provocation diameter of the distal segment of the infarct-related artery predicted coronary spasm whereas atenolol did not. ConclusionsThis study showed that atenolol 50 mg/day did not increase coronary spasm in Japanese acute MI patients. It is suggested that beta-blockers can be safely used soon after coronary intervention for acute MI without the risk of increasing coronary spasm; however, attention should be paid to hemodynamic change in the acute phase.

Acute beta-adrenoceptor blockade improves efficacy of ibutilide in conversion of atrial fibrillation with a rapid ventricular rate

Activation of beta-adrenoceptors attenuates prolongation of action potential duration induced by blockade of the delayed rectifier potassium current. We examined whether acute administration of beta-blocker could enhance ibutilide (IB) efficacy in conversion of atrial fibrillation (AF) with a rapid ventricular rate. Ninety patients (aged 63 +/- 13.5 years) with rapidly conducting AF were randomized in to two groups. Group A (n = 44) received esmolol titrated to achieve a heart rate of <100 bpm followed by IB co-administration, while Group B (n = 46) were treated with IB as monotherapy. In Group A, 29 patients (67%) converted to sinus rhythm (SR) compared with 21 (46%) in Group B (P = 0.04). The use of esmolol was the most important predictor for cardioversion (P = 0.009). The slower the heart rate at the time of IB initiation, the higher the likelihood for cardioversion (P = 0.015). Patients in Group A had significantly shorter corrected QT interval (QTc) at the time of conversion than those in Group B (433 vs. 501 ms, P = 0.003). Two patients in Group A developed severe bradycardia, whereas three patients in Group B developed severe ventricular tachycardia (VT). Compared with IB monotherapy, the combination therapy of esmolol and IB appears to be more effective in conversion of rapidly conducting AF back to SR. The addition of beta-blocker reduces QTc prolongation and diminishes the risk of VT at the expense, however, of increased bradycardic events.

Peyronie Disease in Association with Carvedilol: A Case Report

Beta blockade is associated with the onset and progression of Peyronie disease (PD). To date, there has not been a report of PD occurring with the alpha/beta blocker carvedilol. It remains unproven but likely that carvedilol was the cause of the PD in the patient described in this case. It is hypothesized that because of carvedilol's vasodilating alpha adrenergic receptor stimulation and its anti-inflammatory effect, PD occurs less frequently with carvedilol than with other beta blockers. However, in this case the protective properties of carvedilol, like vasodilation and the anti-inflammatory effect, may not be sufficient to overcome its vasoconstricting beta adrenergic receptor blockade.