No abstract

Micturition and bladder responsiveness in vitro were impaired in rats fed isotonic sucrose, afflicted with diabetes mellitus or diabetes insipidus. Their urinary output which was seven times control, initiated micturition responses at volumes three times control. Nerve-induced contractions by bladders from these rats developed substantially less pressure than control. Contractions elicited at 1 Hz by control and impaired bladders were potentiated equally by tetraethylammonium chloride (TEA) (5 mM) or by carbachol (2 X 10(-7) M). Contractions elicited at 20 Hz by normal bladders were not potentiated, those by impaired bladders were. TEA, by increasing transmitter release, and carbachol, by a postjunctional action, substantially reversed bladder dysfunction. Because control and impaired bladders were equally enhanced by TEA, prejunctional and contractile element (CE) activity at 1 Hz were probably unaffected by distension. However, postjunctional sensitivity was probably reduced. Impaired bladders, more compliant than controls, became less compliant after carbachol without elevating resting pressure. Whereas the action of carbachol to enhance bladder responsiveness did not involve tension development, there may have been cholinoceptor facilitation and shortening of CE.

1. Type A or type D botulinum toxin administered to rats did not produce a generalized paralysis of skeletal muscles at the time of ventilatory arrest. However, if survival was extended by artificial ventilation complete blockade of neuromuscular transmission developed 6.5 hr after 100 MLD of type D and 5 hr after 1000 MLD of type A toxin. The onset of paralysis of a muscle was shortened by repetitive stimulation of the motor nerves.2. There was no consistent blockade of parasympathetically innervated viscera in animals dying after type A toxin. Animals given type D toxin displayed mydriasis and urinary retention before death.3. Motor responses to electrical stimulation, of bladder preparations in vitro were more vulnerable to type D than to type A toxin. When somatic paralysis was complete in animals treated with type A or type D toxin the excised bladders produced pressure elevations 45 and 25%, respectively, of control preparations.4. During electrical stimulation of bladder preparations nearly paralysed by either toxin, the ACh release was significantly diminished from controls. In the rat bladder botulinum toxin specifically disrupted the liberation of mediator from post-ganglionic nerve endings.

1The action of an anticholinesterase and an antimuscarinic drug upon nerve-induced contractions of the rat urinary bladder were examined during transmural stimulation at 20 Hz. Responses were graded in magnitude by limiting the duration of the stimulus trains. 2 Responses of low magnitude produced by short stimulus trains were unchanged by atropine; however, maximal responses resulting from long stimulus trains were diminished in magnitude and shortened in duration. 3 Responses of small magnitude elicited by short stimulus trains involve muscarinic receptors in close proximity to the neuroeffector junction and are resistant to atropine. 4 Maximal responses elicited by long stimulus trains involve'junctional' muscarinic receptors as well as receptors located at the periphery of the junction; the 'extrajunctional' receptors are blocked by atropine. 5Responses of low magnitude produced by short stimulus trains were unaffected by echothiophate; however, the duration of maximal responses resulting from the long stimulus trains was extended. 6 The inhibition of cholinesterase did not increase the occupation of muscarinic receptors by the transmitter; however, after large quantities of transmitter were released by the long stimulus trains the association between the receptors and acetylcholine was prolonged.

SUMMARY1. The post-ganglionic nerves visible in silver-impregnated sections of a normal rat bladder were absent 14 days after both pelvic ganglia had been ablated. After ablation of one ganglion the distribution of nerve trunks in either side of the organ was unchanged. Post-ganglionic axons from either side appear to distribute bilaterally.2. The acetylcholine (ACh) content of the rat bladder was reduced from control by 50 % after the post-ganglionic nerves from one ganglion had degenerated. However, the ACh content in the two halves of the bladder sectioned along the mid line was the same after one nerve had degenerated. 3. Motor responses of bladder preparations elicited during stimulation of both pelvic nerves were compared with responses elicited when each nerve was stimulated separately. In three-quarters of the animals the sum of the individual responses exceeded the response to combined nerve stimulation by no more than 20 %. The functional overlap between the two groups of motor nerves to the bladder was therefore no greater than this amount in most animals.4. Motor responses of normally innervated bladder preparations elicited in vitro by transmural stimulation were compared with responses elicited after the post-ganglionic innervation from one side had degenerated. The mean response of bladders with half their innervation was 50-65°/ % of the mean response of bladders normally innervated. The functional overlap by the two groups of nerves was found to be no greater than 15 %.