Animals ; Arthritis, Experimental ; Collagen Type II ; Male ; Mice ; Mice, Inbred DBA ; Receptors, Adrenergic, alpha-1 ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology*

Kidney is one of the important organs of the body.With both excretory and endocrine functions,it plays a vital role in regulating the normal physiological state.As a precursor of the nitric oxide(NO)synthesis
Animals ; Arginine/physiology* ; Kidney/physiology* ; Muscle, Smooth, Vascular ; Nitric Oxide/physiology* ; Rats ; Receptors, Adrenergic, alpha-1/physiology* ; Renal Insufficiency/physiopathology* ; Signal Transduction ; Vasoconstriction

PURPOSE: To assess the effectiveness of alpha-1 adrenergic receptor blockers (α1-blockers) in the treatment of female lower urinary tract symptoms (LUTS). METHODS: A literature search was conducted using the PubMed/MEDLINE, Embase, and Cochrane Library databases. Fourteen studies with 1,319 patients were ultimately included. The study comprised 2 analyses: a comparison of urinary symptom scores, maximal flow rate (Qmax), and postvoid residual (PVR) urine volume before and after α1-blocker administration in 8 prospective, open-label studies and 5 randomized clinical trials (RCTs); and an evaluation of the same variables in α1-blocker and placebo groups in 4 RCTs.
Female ; Humans ; Lower Urinary Tract Symptoms ; Prospective Studies ; Receptors, Adrenergic, alpha-1

PURPOSE: To evaluate the efficacy of an alpha-1 adrenergic receptor (α1-AR) blocker for the treatment of female voiding dysfunction (FVD) through a pressure-flow study. METHODS: This was a randomized, double-blind, placebo-controlled trial. Women aged ≥18 years with voiding symptoms, as defined by an American Urological Association symptom score (AUA-SS) ≥15 and a maximum flow rate (Qmax) < 15 mL/sec with a voided volume of >100 mL and/or a postvoid residual (PVR) volume >150 mL, were randomly allocated to either the alfuzosin or placebo group. After 8 weeks of treatment, changes in the AUA-SS, Bristol female lower urinary tract symptoms (BFLUTS) questionnaire, Qmax/PVR, and voiding diary were compared between groups. Patients’ satisfaction with the treatment was compared. Patients were categorized into 3 groups according to the Blaivas-Groutz bladder outlet obstruction (BOO) nomogram: none, mild, and moderate to severe. Subgroup comparisons were also made. RESULTS: Of a total of 187 women, 154 (79 alfuzosin, 75 placebo) were included in the analysis. After 8 weeks of treatment, the AUA-SS decreased by 7.0 in the alfuzosin group and by 8.0 in the placebo group. Changes in AUA-SS subscores, BFLUTS (except the I-sum), the voiding diary, and Qmax/PVR were not significantly different between groups. Approximately 54% of the alfuzosin group and 62% of the placebo group were satisfied with the treatment. No significant difference was observed between groups according to the presence or grade of BOO. CONCLUSIONS: Alfuzosin might not be more effective than placebo for treating FVD. The presence or the grade of BOO did not affect the results. A further study with sufficient power is needed to determine the efficacy of α1-AR blockers for the treatment of FVD.
Adrenergic alpha-Antagonists ; Female ; Humans ; Lower Urinary Tract Symptoms ; Nomograms ; Receptors, Adrenergic, alpha-1 ; Urinary Bladder Neck Obstruction ; Urodynamics

PURPOSE: The urinary bladder (UB) is innervated by both sensory and autonomic nerves. Recent studies have shown that sensory neuropeptides induced contractions in the detrusor muscle. Therefore, in a mouse model, we investigated the presence of interactions between the submucosal sensory nerves and the autonomic nerves that regulate the motor function of the detrusor muscle. METHODS: UB samples from male C57BL/6 mice were isolated, cut into strips, and mounted in an organ bath. Dose-response curves to norepinephrine and phenylephrine were studied in UB strips with and without mucosa, and the effects of preincubation with a receptor antagonist and various drugs on relaxation were also studied using tissue bath myography. RESULTS: Phenylephrine-induced relaxation of the UB strips showed concentration-related effects. This relaxation appeared in both mucosa-intact and mucosa-denuded UB strips, and was significantly inhibited by lidocaine, silodosin, and guanethidine (an adrenergic neuronal blocker). Meanwhile, phenylephrine-induced relaxation was inhibited by pretreatment with propranolol and calcitonin gene-related peptide (CGRP)–depletory capsaicin in UB strips with and without mucosa. CONCLUSIONS: The present study suggests that phenylephrine activates the α-1A adrenergic receptor (AR) of the sensory nerve, and then activates capsaicin-sensitive sensory nerves to release an unknown substance that facilitates the release of norepinephrine from adrenergic nerves. Subsequently, norepinephrine stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the UB. Further animal and human studies are required to prove this concept and to validate its clinical usefulness.
Adrenergic Neurons ; Animals ; Autonomic Pathways ; Baths ; Calcitonin Gene-Related Peptide ; Capsaicin ; Guanethidine ; Humans ; Lidocaine ; Male ; Mice ; Mucous Membrane ; Myography ; Neuropeptides ; Norepinephrine ; Phenylephrine ; Propranolol ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-1 ; Relaxation ; Urinary Bladder*

PURPOSE: The aim of this study was to assess the potential involvement of a specific subtype of 5-hydroxytryptamine (5-HT), 5HT(2) receptors in neurally-induced contractions of the human detrusor. METHODS: Contractile responses to electrical field stimulation (EFS) were examined in human isolated urinary bladder muscle strips. The potentiation of EFS-induced detrusor contraction was examined by adding cumulative concentrations of a 5-HT and 5-HT(2) receptor agonist, α-methyl-serotonin (α-Me-5-HT) (1nM–100μM) in the presence or absence of a 5-HT₂ antagonist, ketanserin (5-HT(2A)>5-HT(2C)) or naftopidil (5-HT(2B)>5-HT(2A)) (0.3–3μM). RESULTS: 5-HT and α-Me-5-HT potentiated EFS-induced contraction with a maximal effect (E(max)) of 37.6% and 38.6%, respectively, and with pEC(50) (negative logarithm of the concentration required for a half-maximal response to an agonist) values of 8.3 and 6.8, respectively. Neither ketanserin nor naftopidil at any concentration produced a rightward displacement of the α-Me-5-HT concentration response curve. Instead, the E(max) of α-Me-5-HT increased in the presence of ketanserin at 0.3–1μM and in the presence of naftopidil at 1μM to 51% and 56%, respectively, while the E(max) in the presence of vehicle alone was 36%. The highest concentration (3μM) of either drug, however, fully reversed the enhancement. CONCLUSIONS: The potentiating effect of α-Me-5-HT on neurally-induced contraction of human urinary bladder muscle strips was not found to be mediated via any 5-HT(2) receptor subtypes. The underlying mechanism for the enhancement of the α-Me-5-HT potentiating effect on detrusor contractility by ketanserin and naftopidil remains unknown; however, our results suggest that these drugs may be useful for treating contractile dysfunction of the detrusor, as manifested in conditions such as underactive bladder.
Humans* ; Ketanserin* ; Prostatism ; Receptors, Adrenergic, alpha-1 ; Receptors, Serotonin ; Serotonin ; Urinary Bladder Neck Obstruction ; Urinary Bladder*

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Animals ; Cells, Cultured ; Cytokines/immunology ; Fibroblasts/immunology/pathology ; Humans ; Lipopolysaccharides/administration & dosage/immunology ; Male ; Periodontal Ligament/cytology/immunology/pathology ; Periodontitis/*drug therapy/*etiology/immunology/pathology ; Phentolamine/*therapeutic use ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-1/analysis/*immunology ; Signal Transduction/drug effects ; *Stress, Physiological/drug effects ; Tyrosine 3-Monooxygenase/analysis/immunology

PURPOSE: To investigate the effects of estrogen on the expression of the alpha1 receptor and nitric oxide synthase (NOS) in rat urethra and bladder after oophorectomy. MATERIALS AND METHODS: Forty-five mature female Sprague-Dawley rats (aged 10-11 weeks, 235-250 g) were randomly assigned to one of three groups: control group, oophorectomy group (Opx), or oophorectomy and estradiol replacement group (Opx+ Est). The degree of expression of alpha1 receptor (alpha1A and D) and NOS (neuronal NOS [nNOS] and endothelial NOS [eNOS]) in bladder and urethral tissues was investigated by using immunohistochemical staining and Western blotting. RESULTS: In the bladder, the expression rates of alpha1 receptor (alpha1A and alpha1D) increased in the Opx group but decreased in the Opx+Est group. These changes were not statistically significant. The alpha1A and alpha1D receptor of the urethra decreased in the Opx group but increased in the Opx+Est group. These changes were not statistically significant. In the bladder and urethra, the expression rates of nNOS and eNOS significantly increased in the Opx group but decreased in the Opx+Est group (p<0.05). CONCLUSIONS: These data suggest that estrogen depletion increases NOS and alpha1 receptor expression in the rat bladder. However, these changes could be restored by estrogen replacement therapy.
Animals ; Collagen/metabolism ; Estradiol/analogs & derivatives/blood/pharmacology ; Estrogen Replacement Therapy/*methods ; Female ; Muscle, Smooth/pathology ; Nitric Oxide Synthase/*metabolism ; Ovariectomy ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1/*metabolism ; Urethra/drug effects/*metabolism/pathology ; Urinary Bladder/drug effects/*metabolism/pathology

OBJECTIVETo observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.

METHODSThe isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.

RESULTSAKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P<0.05), reduced contractile wave amplitude (r=0.837, P<0.05) and decreased contractile frequency (r=-0.917, P<0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.

CONCLUSIONAKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing &alpha;1-adrenergic receptors and M-cholinergic receptors.

Animals ; Calcium Chloride ; pharmacology ; Carbachol ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Hydroxylamines ; pharmacology ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Neuromuscular Agents ; pharmacology ; Prostate ; drug effects ; physiology ; Rabbits ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Muscarinic ; metabolism ; Urethra ; drug effects ; physiology ; Urinary Bladder ; drug effects ; physiology

mRNAs of alpha-adrenoceptor (&alpha;-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of &alpha;-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that &alpha;1A-, &alpha;1B-, and &alpha;2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. &alpha;1D- and &alpha;2C-AR was also expressed in all size neurons in normal DRG. However, &alpha;1D-AR was significantly increased and &alpha;2C-AR was decreased in small size neurons 14 days post CCI. &alpha;2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of &alpha;1A- and &alpha;2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of &alpha;-AR subtypes in DRG neurons, and the distribution and levels of expression of &alpha;-AR subtypes change differently after CCI. The up-regulation of &alpha;-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.
Animals ; Cell Size ; Chronic Disease ; Constriction, Pathologic ; Fluorescent Antibody Technique ; Ganglia, Spinal ; metabolism ; pathology ; Male ; Microscopy, Confocal ; Neurons ; metabolism ; pathology ; Pain Measurement ; methods ; Pain Threshold ; Protein Isoforms ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1 ; metabolism ; Receptors, Adrenergic, alpha-2 ; metabolism ; Sciatic Nerve ; injuries ; surgery