| Urinary bladder function is affected by many factors, such as regulations by the autonomic nervous system and somatic nervous system, contractile or relaxant condition of the detrusor smooth muscle, tension of the prostate smooth muscle and so on. Available literature indicates that the mouse prostate has similar innervations to humans and other laboratory animals, and the responses to nerve stimulation are noradrenergic and mediated byα1-adrenoceptors. The mouse prostate is a suitable model for human prostate function and a viable isolated preparation for contractility studies. Moreover, the M3 muscarinic receptors are the predominant receptor mediating cholinergic-induced urinary bladder contractility in the mouse being comparable to the human urinary bladder. It was reported that estrogen and chemotherapy drugs were able to affect the urinary bladder micturition of the anesthetized mouse. Development and evaluation of in vivo mouse model are very important in elucidating the integrated action in whole animals with only a small amount of agents and in screening of drug candidate. Sympathetic and parasympathetic nervous systems play a key role in regulating the function of storage and micturition of urinary bladder. Therefore, in the present experiments we observed for the first time the effects of intravenous administration ofα1-adrenergic,β-adrenergic or muscarinic cholinergic agonist, andα1-adrenergic antagonist as first-line therapy for patients with benign prostatic hyperplasia on the urinary bladder micturition function in the anesthetized mouse.Aim: To observe effects of intravenous administration of phenylephrine, isoprenaline, carbachol and doxazosin on the urinary bladder micturition function in the anesthetized mouse, and analyze the pharmacological characteristics of the agents.Methods:1. Male mouse was anaesthetized with urethane (1.5g·kg-1), then a catheter was inserted into trachea to allow drainage of bronchial secretion and to facilitate the breath. The tail vein was cannulated for drug administration. A small incision was made in the lower abdomen, and the ureters were cut off. The distal ends of the ureters were ligated and a cotton wool ball was placed on the proximal ends to absorb urine. For bladder pressure measurements, a cannula (22GA×1.0IN) was inserted through the bladder apex into the lumen. Room temperature was kept at 25-30℃during experiments. After obtaining a control cystometrogram we injected agents into the tail vein, then vesical micturition pressure (VMP), micturition threshold pressure (MBP), intercontraction interval (ICI) and micturition time (MT) were recorded. 2. Male mouse was anaesthetized with urethane (1.5g·kg-1), then a catheter was inserted into trachea to allow drainage of bronchial secretion and to facilitate the breath. The tail vein was cannulated for drug administration. A venoclysis needle (0.55mm) filled with physiological saline including 350U·ml-1 heparin was inserted into the left common carotid artery for blood pressure measurement. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) were monitored via the venoclysis needle connected to a pressure transducer, and displayed on PowerLab/8sp through computer running the PowerLab Chart 5.0 software.Results:1. Effects of phenylephrine, carbachol, isoprenaline and doxazosin on the micturition function of the urinary bladder in the anesthetized mouseVMP, MTP, MBP, ICI and MT in the solvent control group did not change significantly (P>0.05) after intravenous administration of physiological saline.Phenylephrine administered intravenously (50~800μg·kg-1) increased the VMP in the anesthetized mouse in a dose-dependent manner in comparison with before drug (P<0.05, P<0.01). The value of MBP was increased by phenylephrine at 800μg·kg-1 in comparison with before drug (P<0.05). Phenylephrine did not change MTP, ICI and MT significantly (P>0.05) in the anesthetized mouse. In the animals treated with carbachol (3.0~7.0μg·kg-1), MBP value was significantly (P<0.01) increased by carbachol at 7.0μg·kg-1, and the values of ICI and MT were significantly (P<0.05,P<0.01) increased by carbachol at 6.0 and 7.0μg·kg-1 in comparison with before drug. Carbachol slightly but not significantly (P>0.05) increased the VMP and it did not affect the MTP in the anesthetized mouse.Isoprenaline at 1000μg·kg-1 administered intravenously in the anesthetized mouse significantly decreased the VMP in comparison with before drug (P<0.05), and it increased the MT significantly (P<0.05, P<0.01) at doses of 300 and1000μg·kg-1. The values of MTP, MBP and ICI were not affected by isoprenaline significantly (P>0.05).Doxazosin (10~1000μg·kg-1) administered intravenously did not significantly (P>0.05) affect any of the parameters in the cystometrogram in the anesthetized mouse.2. Effects of doxazosin on phenylephrine-induced increase in the vesical micturition pressure in the anesthetized mousePhenylephrine 220μg·kg-1 was administered intravenously for 6 times in the solvent control group, and it increased the VMP significantly at each time. The increased VMP by phenylephrine was not significantly (P>0.05) affected by administration of physiological saline in comparison with the control value (the third time). Doxazosin at 0.3 and 1.0 mg·kg-1 significantly (P<0.01) decreased phenylephrine-induced increase in VMP in a dose-dependent manner in the anesthetized mouse.3. Effects of phenylephrine, carbachol, isoprenaline and doxazosin on the blood pressure in the anesthetized mouseIntravenous administration of carbachol 7.0μg·kg-1, doxazosin 1mg·kg-1 or isoprenaline 1mg·kg-1 significantly decreased the SBP, DBP and MABP in the anesthetized mouse. The percentage value of maximal decease in SBP, DBP or MABP by carbachol was not significantly (P>0.05) different from that by doxazosin and by isoprenaline, respectively. Carbachol and isoprenaline decreased the blood pressure transiently, but doxazosin had a long-lasting hypotensive effect in the anesthetized mouse. Phenylephrine significantly (P<0.01) and transiently increased the SBP, DBP and MABP in the anesthetized mouse.Conclusion: In the anesthetized mouse, activation of muscarinic receptors decreases the voiding frequency and increases the urine storage volume and VMP, activation ofα1-adrenergic receptors increases the VMP mainly, and activation ofβ-adrenergic receptors decreases the VMP and prolongs MT. Doxazosin, anα1-adrenergic antagonist, does not affect the urinary bladder micturition function by itself, however it antagonizes phenylephrine-induced increase in VMP in the anesthetized mouse. |
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