The Effects of Pyridostigmine and Levosulpiride on the Contraction of Rabbit Urinary Bladders / 대한비뇨기과학회지

PURPOSE: This study was performed to identify the effects of bethanechol, pyridostigmine and levosulpiride, on the contraction of rabbit bladder strip tissue in a single agent administration, and to investigate the synergistic effects in a mixed administration. MATERIALS AND METHODS: Smooth muscle strips of bladder were prepared using female, New Zealand white, rabbits. After an equilibration period, dose response curves to each agent, with cumulative administration, were performed in the basal tension state of the strips. Each strip was then pretreated with the agent at the maximal concentration that would not induce a bladder contraction, and second dose-response curves for the other agents were obtained. Following this, the maximal stimulation with bethanechol was performed, and during the tonic response, pyridostigmine or levosulpiride was administrated to observe any synergistic effects of the agents. Similar experiments were repeated for the pyridostigmine and levosulpiride. RESULTS: Each agent elicited a dose-dependent contractile response, in the order; bethanechol (0-4.49g/100mg tissue), pyridostigmine (0-1.58g/100mg tissue) and levosulpiride (0-0.44g/100mg tissue). In the presence of pyridostigmine (3x10(-6)M) or levosulpiride (10(-4)M), no additive effects were noted after the cumulative stimulation with bethanechol (10(-10)-10(-4)M). During the tonic response of bethanechol (10(-4)M) or pyridostigmine (10(-2)M), the addition of levosulpiride (10(-2)M) induced a significant increase in the bladder strip contractions, but the addition of pyridostigmine (10(-2)M) or bethanechol (10(-4)M) decreased the maximal response (p<0.05). CONCLUSIONS: These results imply that pyridostigmine may be useful for impaired detrusor contractility management. Synergistic effects can also be expected when administrating levosulpiride, in addition to bethanechol, in improving bladder contractility.

Altered Contractility of the in vivo Feline Trabecular Smooth Muscle under Acidosis / 대한비뇨기과학회지

PURPOSE: Previous studies concerning the ischemic priapism revealed that hypoxia alter the erectile and contractile responses of penis. But the effects of accompaning acidosis on the trabecular smooth muscle contractility have not been fully evaluated or understood yet. We performed this study to elucidate the role of acidosis on the trabecular smooth muscle contractility like in ischemic priapism. MATERIALS AND METHODS: Under the general anesthesia, 55 mature male cats were conditioned to systemic metabolic acidosis by hypoventilation with animal ventilator. The changes of intracavernous pressure to erectics(acetylcholine, L-arginine, PGE1), erectolytics(epinephrine, TXA2), K+-channel-related drugs (pinacidil, 4-aminopyridine, TEA, glibenclamide) and calcium ionophore were monitored at Set 1 (PO2>60mmHg, pH>7.25), Set 2(PO2 pH>7.0), Set 3(PO260mmHg, pH<7.0) in vivo. RESULTS: At Set 1 and Set 2, the acetylcholine or PGE1-induced relaxations were suppressed by epinephrine, TXA2 or ionomycin(n=9, p<0.01). The contractility was in order of epinephrine, TXA2 and ionomycin. Cavernous relaxations to acetylcholine or PGE1 were reduced by acidosis(n=8, p<0.01). TXA2 or ionomycin did not produced contraction even with higher concentration but epinephrine maintained contractility with higher concentration at acidosis (n=7, p<0.05). Acidosis-induced relaxation was not prevented by 4-aminopyridine, TEA, or glibenclamide(n=6, p<0.05). Pinacidil did not induced relaxation at acidosis(n=6, p<0.01). CONCLUSIONS: Acidosis impairs the contractile response of cavernous smooth muscle to submaximal stimulation with erectolytics. It may be the results of the interference by(H+) with the intra and extracellular mechanisms that regulate the homeostasis of(Ca2+). Conclusively, acidosis is another limiting factor of trabecular smooth muscle contractility like in ischemic priapism.

Effect of Ethanol on the Contractility of the Muscle Strips of the Bladder Neck in the Rabbit / 대한비뇨기과학회지

PURPOSE: Ethanol is known to induce bladder neck contraction so that it may cause acute urinary retention in patients with benign prostatic hyperplasia. We investigated whether ethanol has a-sympathomimetic effects in the bladder neck. MATERIALS AND METHODS: 36 New Zealand rabbits weighing from 2.5-3.0kg were used for this experiment. The rabbits were sacrificed by air embolism and the urinary bladder was immediately removed. The urinary bladder was dissected free from surrounding tissues and divided into the bladder body and neck in oxygenated Tyrode's solution. The bladder neck muscle strips were taken and the contractile responses to electrical field stimulation(2, 4, 8, 16 and 32Hz) and phenylephrine(1 mM), adenosine triphosphate(ATP, 100mM) and KCI(100mM)were measured. RESULTS: The frequency-response curve by electrical stimulation in ethanol pretreated Tyrode's solution were attenuated, but tonic contractions were not affected. ATP induced contraction was also attenuated. Ethanol showed relaxing effects in the contractile responses elicited by phenylephrine and KCI. CONCLUSIONS: From these studies, ethanol is shown to exert direct inhibitory action on bladder neck contraction presumably by lowering the calcium sensitivity of the smooth muscle in the rabbit.

Effects of ketamine on contractile responses in vascular smooth muscle

This study was designed to determine the effects of ketamine on contractions induced by norepinephrine (NE), K+ or histamine (Hist) and on agonist-induced calcium mobilization, in rabbit thoracic aorta with or without endothelium. Contractile responses to NE, K+ or Hist were markedly attenuated by prior exposure to ketamine. Subsequent addition of ketamine to the rabbit aorta undergoing an isometric contraction induced by NE, K+ or Hist also decreased the contractile responses in a calcium ion concentration-dependent manner. Preincubation with ketamine produced a concentration-dependent inhibition of contractile responses elicited by the addition of calcium ion (1.6 mM) to a Ca(++)-free depolarizing solution. However, the phasic contraction produced by NE with 2mM lanthanum pretreatment, which is release of intracellular calcium, was also inhibited by ketamine. Moreover, the tonic contraction produced by NE after depletion of the agonist-releasable pool of intracellular calcium, which is thought to be due to calcium influx, was depressed by ketamine. These data suggest that ketamine relaxes NE-contracted rings of rabbit thoracic aorta by decreasing calcium entry and by producing an extracellular calcium-independent relaxant effect.