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We have studied the effects of intrathecally-injected drugs that act on alpha-adrenoceptors in the urinary bladder reflex contractile activity evoked by continuous infusion of fluid into the bladder of anesthetized rats. Clonidine (10 and 30 micrograms) facilitated and yohimbine (100 micrograms) abolished the bladder contractile activity, and pretreatment with yohimbine (30 micrograms) inhibited the effect of clonidine (10 micrograms). Phenylephrine (60 micrograms) abolished the bladder contractile activity, but prazosin (40 micrograms) had no significant effect on it. The bladder contractions induced by electrical stimulation of the pontine micturition center were inhibited by yohimbine in a dose-dependent manner. These results suggest that transmission in the descending neurons from the pontine micturition center to the sacral parasympathetic neurons that control bladder motility is mediated by alpha 2-adrenoceptors in rats.

In anesthetized rats, SKF 38393 (10 mg/kg, i.v.) did not facilitate urinary bladder motility, but bromocriptine (BR, 5 mg/kg, i.v.) alone and the combination of BR (1 mg/kg, i.v.) and SKF 38393 (1 mg/kg, i.v.) induced a hyperactive bladder response (HBR). Both HBR induced by BR alone or BR and SKF 38393 combined was suppressed by SCH 23390, sulpiride or haloperidol. These results indicate that HBR is mediated by the activation of D-2 receptors, and the effects of D-2 agonists on bladder motility are potentiated by the simultaneous stimulation of D-1 receptors.

Effects of acetylcholine (ACh) on the membrane potential and current recorded from endothelial cells dispersed from the rabbit aorta were investigated using the patch-clamp technique. ACh hyperpolarized the endothelial cell membrane. Using the whole-cell voltage-clamp procedure, ACh (10(-6) M) induced an outward current, and this current was blocked by atropine (10(-6) M). Application of either pirenzepine (3 x 10(-7) M) or AF-DX 116 (3 x 10(-6) M) slightly inhibited the ACh-induced outward current, and simultaneous application of these two blockers markedly inhibited the outward current. Application of caffeine (2 x 10(-2) M), ryanodine (10(-5) M) or heparin (10(-5) g/ml) reduced the amplitude of the ACh-induced outward current. A single-channel current recording using the patch-clamp technique revealed that ACh opens a Ca-dependent K-channel with a single-channel current conductance of 9 pS. These results indicate that both M1 and M2 receptor subtypes are present in endothelial cells of the rabbit aorta and that ACh activates the Ca-dependent K channel via release of Ca from intracellular store sites. In addition, methylene blue inhibited the ACh-induced outward current from the outside membrane.

We studied the effects of drugs used for treatment of bladder dysfunction in conscious rats with intact pelvic nerves and also in rats at one or two weeks after nerve decentralization on the left side. Bladder contraction accompanying micturition was continuously induced by infusion of solution at a constant rate. When the effects of oxybutynin (3 mg/kg, i.p.) and terodiline (3 and 10 mg/kg, i.p.) on the cystometrogram were studied for about 2 hr, these drugs shortened and then prolonged the micturition interval (MI), but atropine (1 and 5 mg/kg, i.p.), butylscopolamine (20 mg/kg, i.p.) and nifedipine (3 mg/kg, i.p.) exhibited only a shortening effect on the MI. After injection of oxybutynin (10 mg/kg, i.p.), solution dribbled from the urethra for about 30 min. Terodiline (3 mg/kg) caused ischuria in the rats one week after resection of the left pelvic nerve, but not in the rats two weeks after surgery. Physostigmine (0.3 mg/kg, i.p.) improved micturition in the rats one week after surgery, but the effect was not evident in the rats with intact pelvic nerves. It was found that the drugs used for treating failure to store or expel urine exhibited a beneficial effect on micturition in rats with intact pelvic nerves and also in rats one week after nerve decentralization, respectively.

We studied the effect of levcromakalim on the function of the urinary tract in rats. Using anesthetized rats, ureteral peristaltic movement of only the ureter region or the ureter with the kidney was induced by fluid infusion into the ureter lumen. Levcromakalim (0.03 and 0.3 mg/kg, i.v.) exerted a stronger inhibitory effect on the peristaltic movement of the ureter region distant from the pelvis than on that near the pelvis, and the inhibitory effect of levcromakalim (0.03 mg/kg, i.v.) was not antagonized by glibenclamide (0.1 mg/kg, i.v. or 10 mg/kg, i.p.). Topical application of levcromakalim (injection volume, 0.1 ml; 10−4 or 10−3 M), which was injected via a vessel near the ureter inhibited ureteral peristaltic movement and the inhibitory effect levcromakalim (10−4 M), was not antagonized by glibenclamide (10−3 M) injected via the same route. Levcromakalim (0.3 mg/kg, i.v.) did not interrupt micturition in anesthetized and conscious rats. In conscious rats, the micturition interval was prolonged; and in anesthetized rats, the peak pressure during micturition was reduced. After injection of levcromakalim (0.3 mg/kg, i.v.), vesicoureteral reflux did not occur. In the movements of the ureter, urinary bladder and urethra, levcromakalim exerted the strongest inhibitory effect on the ureteral peristalsis.

The oral administration of acetylsalicylic acid(aspirin) elevated serum creatine Phosphokinase(CPK) activity and decreased serum calcium level at 200mg/kg and higher doses in intact rats. The increase of CPK activity was essentially caused by an isozyme, CPK-BB, activity. This effect of aspirin was dose-dependent and more significant in young rats than in old ones. The activities of serum enzymes, GOT, GPT and LDH, remained unchanged in aspirin-treated rats. Both sodium salicylate and 2-thiophenecarboxylic acid, which are hypocalcemie agents, also caused a remarkable elevation of serum CPK activity. The elevation of serum CPK activity by aspirin treatment was inclined to be reduced by calcium chloride treatment. Each oral administration of indomethacin (10mg/kg) and 2,4-dinitrophenol (10mg/kg) failed to change serum CPK activity. These results suggest that the increase of serum CPK activity by aspirin treatment is due to the action of aspirin itself and/or its metabolite, salicylic acid, and is associated with the hypocalcemie action of aspirin but this effect may not be mediated by uncoupling of oxidative phosphorylation and inhibition of prostaglandin synthesis. Furthermore, aspirin seems to have a toxic effect on the organs containing CPK-BB.