Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10⁻⁴ M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A1 receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α₁-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular Ca²⁺ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.
Acetylcholine ; Animals ; Atropine ; Blood Glucose ; Calcium Channels ; Humans ; Injections, Intraperitoneal ; Muscle, Smooth* ; Papaverine ; Prazosin ; Protein Kinase C ; Rats* ; Receptor, Adenosine A1 ; Receptors, Muscarinic ; Streptozocin ; Type C Phospholipases ; Urinary Bladder* ; Verapamil

PURPOSE: Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. METHODS: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively. RESULTS: Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs. CONCLUSIONS: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.
Adult ; Animal Experimentation ; Animals ; Asian Continental Ancestry Group ; Baths ; Excitatory Postsynaptic Potentials ; Humans ; In Vitro Techniques* ; Inhibitory Postsynaptic Potentials ; Injections, Spinal ; Lower Urinary Tract Symptoms ; Male ; Nerve Fibers, Unmyelinated ; Neurons* ; Prazosin ; Prostatic Hyperplasia ; Rats ; Rats, Sprague-Dawley ; Reflex ; Spinal Cord ; Substantia Gelatinosa* ; Urinary Bladder ; Urination

Bladder dysfunction is a common complication of diabetes mellitus (DM). However, there have been a few studies evaluating bladder smooth muscle contraction in DM in the presence of pharmacological inhibitors. In the present study, we compared the contractility of bladder smooth muscle from normal rats and DM rats. Furthermore, we utilized pharmacological inhibitors to delineate the mechanisms underlying bladder muscle differences between normal and DM rats. DM was established in 14 days after using a single injection of streptozotocin (65 mg/kg, intraperitoneal) in Sprague-Dawley rats. Bladder smooth muscle contraction was induced electrically using electrical field stimulation consisting of pulse trains at an amplitude of 40 V and pulse duration of 1 ms at frequencies of 2–10 Hz. In this study, the pharmacological inhibitors atropine (muscarinic receptor antagonist), U73122 (phospholipase C inhibitor), DPCPX (adenosine A₁ receptor antagonist), udenafil (PDE5 inhibitor), prazosin (α₁-receptor antagonist), verapamil (calcium channel blocker), and chelerythrine (protein kinase C inhibitor) were used to pretreat bladder smooth muscles. It was found that the contractility of bladder smooth muscles from DM rats was lower than that of normal rats. In addition, there were significant differences in percent change of contractility between normal and DM rats following pretreatment with prazosin, udenafil, verapamil, and U73122. In conclusion, we suggest that the decreased bladder muscle contractility in DM rats was a result of perturbations in PLC/IP₃-mediated intracellular Ca²⁺ release and PDE5 activity.
Animals ; Atropine ; Diabetes Mellitus ; Muscle, Smooth ; Phosphotransferases ; Prazosin ; Rats* ; Rats, Sprague-Dawley ; Streptozocin ; Type C Phospholipases ; Urinary Bladder* ; Verapamil

Objective: To investigate the short- and long-term effects of triple acupuncture at the Qugu acupoint as an adjunctive therapy on type-Ⅲ chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). METHODS: We equally randomized 90 CP/CPPS patients into a control and a treatment group, both treated with Levofloxacin Mesylate Tablets (0.5 g, tid) + Terazosin Hydrochloride Capsules (2 mg qd) for 4 weeks, while the latter group by triple acupuncture at the Qugu acupoint as an adjunctive therapy twice a week at the same time. Then, we followed up all the patients for 4 weeks, recorded the cases, time and rate of recurrence, obtained the scores in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), quality of life (QoL) and Zung Depression Scale (ZDS), and compared them between the two groups of patients. RESULTS: Compared with the controls, the patients of the treatment group showed significantly decreased NIH-CPSI scores in pain (8.6 ± 2.12 vs 6.2 ± 2.25, P <0.05), micturition (5.8 ± 1.22 vs 3.1 ± 1.10, P <0.05), and QoL (6.0 ± 1.33 vs 3.4 ± 1.71, P <0.05) and ZDS score as well (43.9 ± 4.53 vs 33.6 ± 3.20, P <0.01). The recurrence rate was markedly lower while the recurrence time remarkably longer in the treatment than in the control group (15.56 vs 35.56% and ［20.0 ± 2.72］ vs ［12.5 ± 3.47］ d, P <0.05). CONCLUSIONS As an adjunctive therapy, triple acupuncture at the Qugu acupoint can evidently ameliorate the clinical symptoms, enhance the curative effect of antibacterials, reduce the recurrence rate, and prolong the recurrence time in the treatment of CP/CPPS.
Acupuncture Points ; Acupuncture Therapy ; methods ; Anti-Bacterial Agents ; therapeutic use ; Chronic Disease ; Chronic Pain ; therapy ; Combined Modality Therapy ; Drug Therapy, Combination ; methods ; Humans ; Levofloxacin ; therapeutic use ; Male ; Pelvic Pain ; therapy ; Prazosin ; analogs & derivatives ; therapeutic use ; Prostatitis ; therapy ; Quality of Life ; Recurrence ; Syndrome ; United States ; Urological Agents ; therapeutic use

OBJECTIVEUsing an experimental model of animals exposed to cold to evaluate the regulative effects of prazosin hydrochloride (Pra) and racanisodamine (Ani) on extremital skin temperature of rats and mice.

METHODSEighty animals were randomly divided into eight groups according to the drug dosage. After been administered with drugs by intragastric at room temperature for 60 min, the animals were moved into specified temperature (5 degrees C,18 degrees C) environment and the skin temperatures at the 1/3 site at the proximal end of tail were measured by infrared camera on 180 min and 300 min. Effects of drug were evaluated by changes in tail skin temperatures.

RESULTSPra and Ani combination raised the extremital skin temperature of experimental animals significantly in a dose-dependent manner, while single use of Pra was not potent to rats and less potent to mice, and single use of Ani could not raise extremital skin temperature of both rats and mice. Change of rectal temperature in mice showed that Pra and Ani combination did not affect core temperature.

CONCLUSIONPra and Ani combination could significantly raise extremital skin temperature of rats and mice exposed to cold, and would not affect their core (rectal) temperature.

Animals ; Body Temperature ; Cold Temperature ; Mice ; Prazosin ; pharmacology ; Rats ; Skin Temperature ; drug effects ; Solanaceous Alkaloids ; pharmacology

OBJECTIVETo investigate the changes of vasoconstriction and vasodilatation under different temperature conditions and the protective effects of Vitamin E (Vit E) against endothelial injury induced by hypothermia.

METHODSThe tail arterial rings were prepared for isometric tension recording using multi wire myograph system. The effect of temperature on relaxation and construction was evaluated. Incubate the arterial rings with different concentration of Vit E when they were exposed to hypothermia, then acetylcholine (ACh)-induced endothelium-dependent relaxation was investigated to evaluate the activity of endothelial.

RESULTS(1) The hypothermia could enhanced the dose-dependent construction induced by PE in mice tail artery. (2) Exposure to hypothermia also resulted in increase of sodium nitroprusside (SNP)-induced re-After incubation with Vit E, the vascular relaxation responses to ACh increased in an endothelium-dependent manner, when compared with the hypothermia-treated group.

CONCLUSIONThe vascular function of constriction was attenuated by hypothermia, while the relaxation was increased. Vit E could prevent the hypothermia-induced decrease in vascular endothelial cells.

Animals ; Arteries ; drug effects ; physiology ; Cold Temperature ; Hypothermia ; In Vitro Techniques ; Male ; Mice ; Prazosin ; pharmacology ; Solanaceous Alkaloids ; pharmacology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology ; Vitamin E ; pharmacology

OBJECTIVETo investigate the antithrombotic effects and its molecular mechanisms of prazosin combined with anisodamine (Ani).

METHODSIsolated rat tail artery rings model was employed to evaluate the vasodilative effects of drugs, mice tail thrombosis model induced by carrageenan was used to study the antithrombotic effects and its molecular mechanisms of the drug composition.

RESULTSAmong alpha1-adrenoreceptor antagonists, prazosin(Pra) had the greatest relaxation rate, which was (82.6 +/- 8.9)%, and the EC50 value was 0.44 micromol/L. The drug composition of anisodamine and prazosin of different doses could decrease the length of the tail thrombosis from (24.6 +/- 4.6)mm to (6.9 +/- 2.7)mm, and the rate of thrombosis was decreased from 86.6% to 50.0%. The drug composition could prolong the prothrombin time (PT) distinctively, but it had no effect on the activated partial thromboplastin time (APTT). It also could restrain the decrease of serum levels of tissue plasminogen activator (t-PA) and 6- Keto -PGF1alpha as well as the increase of type-1 plasminogen activator inhibitor (PAI-1) and thromboxane B2 (TXB2) in the mice.

CONCLUSIONThe drug composition formed by anisodamine and prazosin has good effects of relaxing extremities tiny blood vessels and it can fight against thrombosis, its antithrombotic mechanisms may be related to the influence of the extrinsic coagulation pathway, inhibition of platelet activation functions and the promotion of fibrinolysis function.

Adrenergic alpha-1 Receptor Antagonists ; pharmacology ; Animals ; Disease Models, Animal ; In Vitro Techniques ; Male ; Prazosin ; pharmacology ; Rats ; Rats, Wistar ; Solanaceous Alkaloids ; pharmacology ; Thrombosis ; drug therapy

PURPOSE: To investigate the effect of metabolic syndrome (MetS) on the response to medical therapy of benign prostatic hyperplasia (BPH) after a 3-month period of treatment. MATERIALS AND METHODS: This was a cohort study of 100 patients, 47 with MetS and 53 without MetS, referred to either the primary care unit or referral hospital with BPH who had moderate lower urinary tract symptoms of prostate involvement and were candidates for medical treatment. Our main outcome was response to medical treatment with prazosin 1 mg twice a day and finasteride 5 mg daily in patients with BPH on the basis of International Prostate Symptom Score (IPSS). Multivariate analysis of covariance was used to compare BPH treatment response in patients with and without MetS before and after receiving treatment. RESULTS: The mean volume of the prostate was significantly higher in MetS patients than in patients without MetS (57+/-32.65 mL compared with 46.00+/-20.19 mL, p=0.036). The control group demonstrated an 11-unit reduction in IPSS, whereas those with MetS showed a reduction in the symptom score of only 6 units (p<0.001). Regarding the components of MetS separately, triglyceride (p<0.001), fasting blood sugar (p=0.001), and waist circumference (p=0.028) significantly affected the clinical progression of BPH. The observational nature of this study may be a limitation in comparison with an interventional study. CONCLUSIONS: The results of the present study showed that MetS can negatively affect the response to medical treatment of BPH. Therefore, it is necessary to consider MetS in selecting patients with BPH for drug therapy.
Aged ; Case-Control Studies ; Finasteride/*therapeutic use ; Humans ; Lower Urinary Tract Symptoms/etiology ; Male ; Metabolic Syndrome X/*complications ; Middle Aged ; Patient Selection ; Prazosin/*therapeutic use ; Prostatic Hyperplasia/complications/*drug therapy/pathology ; Treatment Outcome ; Urological Agents/*therapeutic use

BACKGROUND: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. METHODS: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. RESULTS: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. CONCLUSIONS: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.
Acute Pain ; Formaldehyde* ; Nefopam* ; Norepinephrine ; Oxidopamine ; Pain Measurement* ; Pain, Postoperative ; Perioperative Period ; Prazosin ; Rats, Sprague-Dawley ; Serotonin ; Spinal Cord ; Yohimbine

BACKGROUND: The effect of spinal adrenergic and cholinergic receptors on the anti-nociceptive effect of intrathecal ginsenosides was determined in a rat postoperative pain model. METHODS: Catheters were placed into the intrathecal space of male Sprague-Dawley rats. Postoperative pain was evoked by an incision to the plantar surface of a hind paw. Withdrawal thresholds was used as a nociceptive parameter and was measured with a von Frey filament. After observing the effect of intrathecal ginsenosides, an alpha-1 adrenergic receptor antagonist (prazosin), an alpha-2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) were given 10 min before administration of the ginsenosides to analyze the contribution of spinal adrenergic and cholinergic receptors on the antinociceptive effect of ginsenosides. RESULTS: Paw incision decreased withdrawal threshold in incised site of paw, but no change of withdrawal threshold was not seen in non-incised site. The intrathecal ginsenosides increased withdrawal threshold of the incised paw in a dose-dependent manner. Pre-treatment with both prazosin and intrathecal yohimbine antagonized the anti-nociceptive effect of the ginsenosides. However, pre-treatments with atropine or mecamylamine had any effect on the antinociceptive activity of ginsenosides. CONCLUSIONS: Intrathecal ginsenosides are effective in attenuation of postoperative pain induced in the rat model. Anti-nociceptive action of ginsenosides is partially mediated by spinal adrenergic receptors, but does not appear to be related to spinal cholinergic receptors.
Animals ; Atropine ; Catheters ; Ginsenosides ; Humans ; Male ; Mecamylamine ; Pain, Postoperative ; Prazosin ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-1 ; Receptors, Adrenergic, alpha-2 ; Receptors, Cholinergic ; Receptors, Muscarinic ; Receptors, Nicotinic ; Spinal Cord ; Yohimbine