OBJECTIVETo demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.

METHODSThe cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.

RESULTS(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.

CONCLUSIONNE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Animals, Newborn ; Cardiomegaly ; chemically induced ; pathology ; prevention & control ; Cell Enlargement ; drug effects ; Cells, Cultured ; Female ; Male ; Myocytes, Cardiac ; cytology ; Norepinephrine ; Prazosin ; pharmacology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Carbazoles/*pharmacology ; Carbon Tetrachloride ; Collagen Type I/drug effects/metabolism ; Cricetinae ; Doxazosin/*pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/chemically induced/*drug therapy ; Liver Function Tests ; Propanolamines/*pharmacology ; Serum Albumin/analysis ; Transforming Growth Factor beta/blood/*drug effects

OBJECTIVETo study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD).

METHODSA prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment.

RESULTSThere were no significant differences in HR, SBP, RR, NE, TNF-&alpha;, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05).

CONCLUSIONSEarly application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.

Adrenergic beta-1 Receptor Antagonists ; therapeutic use ; Child, Preschool ; Female ; Hand, Foot and Mouth Disease ; blood ; drug therapy ; physiopathology ; Humans ; Infant ; Interleukin-6 ; blood ; Male ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Propanolamines ; pharmacology ; therapeutic use ; Prospective Studies ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats.

METHODSHeart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated.

RESULTS(1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol).

CONCLUSIONSbeta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.

Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-Agonists ; pharmacology ; therapeutic use ; Adrenergic beta-Antagonists ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; Male ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Wistar ; Ventricular Remodeling

Benign prostatic hyperplasia (BPH) is a common senile disease, and its main clinical manifestation is lower urinary tract symptom (LUTS), which has long been afflicting old male patients. Previous study showed that alpha1-receptor in the prostate was involved in the development of LUTS. At present, alpha1-receptor blocker is generally accepted as a choice drug for treating BPH and relieving LUTS. The article reviews the tissue distribution of alpha1-receptor and clinical application of alpha1-receptor blocker.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacokinetics ; therapeutic use ; Humans ; Male ; Prostatic Hyperplasia ; drug therapy ; Receptors, Adrenergic, alpha-1 ; analysis

alpha1-adrenoceptor antagonists are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia, while their adverse effects on sexual function are reported frequently in recent years, especially the induction of ejaculatory dysfunction. This review presents the distribution of alpha 1-adrenoceptors in the male genital system and the relationship of alpha1-adrenoceptors with ejaculatory function. It also highlights the interesting phenomenon of ejaculatory dysfunction related to these drugs and its possible mechanism, with the intention to provide some essential clues for further research on this problem as well as some references to safer use of these drugs in clinical settings.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacology ; Ejaculation ; physiology ; Erectile Dysfunction ; chemically induced ; physiopathology ; Humans ; Male ; Receptors, Adrenergic, alpha-1 ; physiology

Hypertension is a rare but well-documented manifestation of neuroblastoma. This is a case in which a hypertensive 8 month-old male with a large left adrenal mass was diagnosed as pheochromocytoma and prepared for surgery with alpha adrenergic blockers and beta adrenergic blockers. Vital signs prior to induction of anesthesia and during surgery also mimicked pheochromocytoma but pathologic examinations revealed neuroblastoma. Laboratory findings also supported pheochromocytoma taking into account the fact that hypertension is rare in neuroblastomas.
Adrenergic alpha-Antagonists ; Adrenergic beta-Antagonists ; Anesthesia ; Child* ; Humans ; Hypertension* ; Infant ; Male ; Neuroblastoma* ; Pheochromocytoma ; Vital Signs

OBJECTIVETo study the biological activities of several alpha1-adrenoceptor antagonists in vitro.

METHODSThe anococcygeal muscle from male Sprague-Dawley rats (300-350 g) was isolated, removed and suspended in a 20-ml organ chamber containing Krebs solution at 37 degrees C, pH 7.4. The muscle preparations were set at a resting tension of 1.0 g and allowed to equilibrate for 1 h in the Krebs solution. After thorough washing, the anococcygeal muscle preparations were examined for the effects of the tested compounds with increased concentrations on its contractile/relaxant responses and the pA2 of antagonistic activity was assessed.

RESULTSSome of the target compounds displayed blocking activity to alpha1-adrenoceptor.

CONCLUSIONCompounds WB IV-1 and WB IV-3 showed good inhibiting activity, and were worth further studying.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; pharmacology ; Anal Canal ; drug effects ; Animals ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Rats ; Rats, Sprague-Dawley

AIMTo establish new methods for the chiral separation and preparation of three new drugs, alfuzosin, terazosin and doxazosin.

METHODSBy optimizing factors which affect the chiral separation, modifier of solvent, chiral additive, pH of mobile phase, modifier of organic base and stationary phase, the optimum condition for chiral separation were selected. The preparation of enantiomers was carried out on semi-preparative reverse phase column (7.8 mm x 250 mm C4 5 microns). Acetonitrile-water modified by the addition of carboxymethyl-beta-cyclodextrin (2%-5%, w/v) was applied as chiral mobile phase.

RESULTSThe enantiomers of three new drugs were base-line-separated and milligram-scale samples of enantiomer were obtained.

CONCLUSIONThe newly established method can be used in research and development of the enantiomers of three new drugs.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Doxazosin ; isolation & purification ; Molecular Structure ; Prazosin ; analogs & derivatives ; isolation & purification ; Quinazolines ; isolation & purification

OBJECTIVESTo evaluate the efficacy of selective alpha 1A-adrenergic receptor antagonists for the treatment chronic abacterial prostatitis/chronic pelvic pain syndrome (CPPS).

METHODSFrom October 2000 to September 2001, a selective alpha 1A-adrenergic receptor antagonists, tamsulosin, had been used in 43 patients with CPPS for four weeks. 0.2 mg dosage was given daily, and uroflowmetry was followed. Symptom scores were evaluated by the NIH-chronic prostatitis symptom index (NIH-CPSI) before and after the treatment.

RESULTSThese patients had a clinically significant response to the treatment of tamsulosin. Of these, thirty two patients (74.5%) responded to one month therapy and had a decrease in NIH-CPSI scores, while maximal urinary flow rate (MFR) and average urinary flow rate (AFR) in patients with poor MFR improved 30.4% and 65.4%, respectively. No severe side effects were observed.

CONCLUSIONSIt is suggested that Tamsulosin, a selective alpha 1A-adrenergic receptor antagonist, is effective in the treatment of CPPS.

Adolescent ; Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; therapeutic use ; Adult ; Chronic Disease ; Humans ; Male ; Middle Aged ; Pelvic Pain ; drug therapy ; etiology ; Prostatitis ; complications ; drug therapy ; Receptors, Adrenergic, alpha-1 ; Sulfonamides ; therapeutic use ; Treatment Outcome