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

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

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

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS). Male Wistar rats were randomly divided into five groups: normal saline control (NS) group, receiving intravenous 0.9% normal saline (5 mL/kg); LPS group, receiving intravenous LPS (10 mg/kg); small-dose dexmedetomidine (S) group, treated with a small dose of dexmedetomidine (0.5 μg · kg(-1) · h(-1)); medium-dose dexmedetomidine (M) group, treated with a medium dose of dexmedetomidine (2.5 μg · kg(-1) · h(-1)); high-dose dexmedetomidine (H) group, treated with a high dose of dexmedetomidine (5 μg · kg(-1) · h(-1)). The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the lungs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio (W/D). The levels of tumor necrosis factor-alpha (TNF-&alpha;) and interleukin-1β (IL-1β) in the lung tissues were assessed by enzyme- linked immunosorbent assay (ELISA). The mRNA and protein expression levels of aquaporin-1 (AQP1) and aquaporin-5 (AQP5) were detected by RT-PCR, immunohistochemistry, and Western blotting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-&alpha; and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group (P<0.01). The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group (P<0.01). Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.
Acute Lung Injury ; chemically induced ; drug therapy ; genetics ; pathology ; Adrenergic alpha-2 Receptor Agonists ; pharmacology ; Animals ; Aquaporin 1 ; agonists ; genetics ; immunology ; Aquaporin 5 ; agonists ; genetics ; immunology ; Dexmedetomidine ; pharmacology ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Gene Expression Regulation ; Injections, Intravenous ; Interleukin-1beta ; antagonists & inhibitors ; genetics ; immunology ; Lipopolysaccharides ; Lung ; drug effects ; immunology ; pathology ; Male ; Organ Size ; drug effects ; Pulmonary Edema ; chemically induced ; drug therapy ; genetics ; pathology ; Rats ; Rats, Wistar ; Signal Transduction ; Transcription, Genetic ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; genetics ; immunology

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

Doxazosin, a high selective alpha1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with benign prostatic hyperplasia (BPH) and also produce several side effects in cardiovascular system. In this study, we observed the isometric vasoconstrictive responses of the rabbit isolated arterial rings to electric field stimulation and noradrenaline ( NA ) to study the effects of R-doxazosin ( R-DOX ) and S-doxazosin ( S-DOX ) on the alpha1-adrenoceptor-regulated vasoconstrictive responses in the rabbit isolated ear artery, mesenteric artery and pulmonary artery, and the effects of higher concentration of S-DOX and R-DOX on presynaptic alpha2-adrenoceptor-regulated purinergic vasoconstriction in the rabbit isolated saphenous artery. We found that R-DOX and S-DOX competitively inhibited the vasoconstriction induced by NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery. The pA2 values of R-DOX and S-DOX against NA in the rabbit isolated ear artery, mesenteric artery and pulmonary artery were 7. 91 +/- 0. 03 and 7. 53 +/- 0. 05, 7. 80 +/- 0. 05 and 7. 29 +/-0. 07, 8. 32 +/- 0. 06 and 7. 97 +/- 0. 07, respectively. The pA2 values of R-DOX in the three arterial preparations were significantly higher than those of S-DOX (P < 0. 01). R-DOX and S-DOX at the concentrations of 0. 1 - 10 micromol x L (-1) did not affect the vasoconstriction induced by electric stimulation in the rabbit isolated saphenous artery. R-DOX and S-DOX at 100 micromol x L(-1) in the rabbit isolated saphenous artery completely inhibited the vascular responses to exogenous NA, but did not affect the vascular responses to exogenous adenosine triphosphate (1 mmol x L(-1) ). It is reasonable to suggest that R-DOX and S-DOX competitively inhibit the vasoconstriction induced by NA in the rabbit ear artery, mesenteric artery and pulmonary artery, and the pA2 values of S-DOX are significantly lower than those of R-DOX. The higher concentration (10 micromol x L(-1)) of R-DOX and S-DOX does not affect the presynaptic alpha2-adrenoceptors at sympathetic nerve terminals of the rabbit saphenous artery.
Adrenergic alpha-2 Receptor Antagonists ; Adrenergic alpha-Antagonists ; chemistry ; pharmacology ; Animals ; Blood Vessels ; drug effects ; physiology ; Dose-Response Relationship, Drug ; Doxazosin ; chemistry ; pharmacology ; Electric Stimulation ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Norepinephrine ; pharmacology ; Pulmonary Artery ; drug effects ; physiology ; Rabbits ; Receptors, Adrenergic, alpha-2 ; physiology ; Stereoisomerism ; Vasoconstriction ; drug effects

The epidemiological survey shows that primary hypertension is one of the independent risk factors in the development and the progress of BPH, 25 percent of old male patients aged 60 or more suffer from the two diseases at the same time, which grievously affects their quality of life. There is little literature about the appropriate therapeutic regimen of BPH associated hypertension. The article reviews the progress in the studies of alpha1-adrenoceptor blocker for BPH associated hypertension, and explores the main problems facing us and ventures the prospects for the development in this field.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; therapeutic use ; Aged ; Aged, 80 and over ; Humans ; Hypertension ; complications ; drug therapy ; Male ; Middle Aged ; Prazosin ; adverse effects ; analogs & derivatives ; therapeutic use ; Prostatic Hyperplasia ; complications ; drug therapy

PURPOSE: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.
Adrenergic alpha-1 Receptor Antagonists/*administration & dosage/therapeutic use ; Adrenergic alpha-Antagonists ; Dose-Response Relationship, Drug ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia/*complications ; *Quality of Life ; Sulfonamides/*administration & dosage/therapeutic use