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Related post: responds to nicotin in the usual manner. The effects on Buy Losartan Online the Auerbach ganglia can also be located; these are stimulated by atropin and nicotin; these and the other autonomic poisons also act more peripherally. Peripheral Reflexes in Other Organs. The intestines are the most prominent, but by no means the only, example of reflex response in the absence of central innervation. In fishes and amphibians, for instance, the iris of the excised eye responds to light, even after removal of the retina (Steinach, 1892); blood vessels regain their tone when their nervous connections degenerate, etc. These reflexes do not even involve the presence of peripheral nerve cells. They may be considered as survivals of the reflex mechanism of the lower invertebrates (Parker, 1909). This conception may Order Losartan help to elucidate some obscure pharmacologic phenomena. Extrinsic Innervation of the Intestine. Sympathetic nerves, running through the superior and inferior splanchnic and mesenteric ganglia, supply the whole tract, from the cardia to the anus, mainly with Purchase Losartan Online inhibitory fibers. The parasympathetic supply consists of the augmentory erigens and pelvic nerves to the anus, rectum and colon; and the vagus fibers, distributed from the esophagus to the end of the ileum. The vagus innervation causes a short primary inhibition, followed by marked stimulation. It is not known whether the extrinsic nerves connect with the local nerve cells; or whether they act independently on the muscle; or both. The bulbo- sacral innervation seems useful mainly for initiating tone, which is then maintained by the local mechanism. The initial inhibition fayors the ingress of the chyme (Cannon, 1911). The "roll movements" which propel the contents for long distances, are of extrinsic origin, due to vagus stimulation with simultaneous depression of sympathetic inhibition (Meltzer and Auer, 1907). Differences of Rhythm at Various Levels. In intact animals, the rhythm is faster toward the two ends of the intestine than toward the middle. In excised intestine, the rate decreases with the distance from the pylorus, the rate of Generic Losartan the duodenum in rabbits being about 50 per cent, faster than in the lower ileum. The oral end is more irritable and therefore acts as pacemaker. It is also less subject to epinephrin relaxation. Its tone is also higher. On the other hand, the slower rate of the aboral end is accompanied by greater excursions (Alvarez, 1914, 1915). The Intrinsic Neuro-muscular Mechanism. The segmentation (pendulum) move- ments and the ordinary peristaltic movements are entirely of peripheral origin, since they are observed also in the excised intestine even when the mucosa and submucosa are removed. They are originated peripheral to the ganglia; for they persist, under suitable conditions, for five days after death, when the ganglia Cheap Losartan must be dead; Buy Cheap Losartan and they can Buy Losartan also be evoked in preparations from which the ganglia have been removed anatomically (Gunn and Underbill, 1914). The rhythmic segmentation movements are automatic, the peristaltic movements are evoked reflexly (as in the Bayliss-Starling reflex; a pinch causes the intestine to constrict for i or 2 cm. above, and to relax for some 30 cm. below the stimulus). The local nerve-muscle mechanism for these reflexes consists of the longitudinal and circular muscular coats, innervated by Auerbach's plexus of nerve cells and fibers, which lies between them. This communicates also with Meissner's plexus in the submucosa, which innervates the glands, muscularis mucosae, etc., but which is not concerned in the intestinal movements. Isolation of Intestinal Coats. Magnus, 1904, found that the muscular coats of the cat's intestine could be separated into layers, so as either to retain or eliminate Auer- bach's plexus. PERIPHERAL AUTONOMIC SYSTEM 275 The "plexus preparations" contain the peripheral nerve cells, and respond to con- tinued stimulation by rhythmic contractions. The plexus-free preparations (which contain only the nerve-endings and muscle) ordinarily respond to continued stimulation by a single tetanic contraction, like ordi- nary smooth muscle; but if the preparations are carefully protected against injury, they also resume spontaneous rhythmic movements after a time (Gunn and Underbill, 1914). With the disappearance of spontaneous movements by exposure, the reaction to all drugs, even barium, is abolished. The response to pilocarpin and 'atropin disappears before that for epinephrin or barium, indicating that the parasympathetic innervation dies before the sympathetic (Gunn and Underbill). The muscularis mucosee also contracts, especially in the diagonal direction. Its rhythm is slow, rather similar to that of the spleen. Its tone and rhythm are increased by epinephrin. Barium causes marked tonic contraction, abolishing the rhythm (Gunn and Underbill). Localization of the Action of Poisons on the Intestine. The use of excised intestine, and of plexus and plexus-free preparations, aids in the localization Order Losartan Online of the action of poisons. If a given action occurs in the excised intestine, the point of attack must be local. If the action occurs in plexus preparations, and not in plexus-free strips, it must be on the ganglion cells. If it occurs in the plexus-free preparations, it must be on the endings or muscle. No reli- able method has been found to distinguish between the nerve-endings and muscle; or between the endings of the extrinsic and intrinsic system, if the two be distinct. All conclusions as to these are based on the insecure ground of analogy. This general method as outlined only discovers the most peripheral point of attack, which is practically the most important; but it does not exclude that the poison may also affect more central structures at the same time. This possibility is not merely theoreti- cal; for even this method shows that the same drug may attack different structures, according to the dose and other conditions. The conditions have not been Losartan Online fully ana- lyzed, and Purchase Losartan until this has been done, the localization of the intestinal phenomena must be rather unsatisfactory. The following exposition is mainly along the lines laid down by Magnus (the Ergebnisse der Physiologic, vol. 7, 1908, and vol. 2, 1903), and by Hans Meyer (Meyer and Gottlieb's Lehrbuch). Action of Drugs on the Intestinal Movements. Barium salts provoke very violent contraction; the effect occurs in plexus-free preparations and is presumably (from anal- ogy) exerted directly on the contractile substance. It is abolished only by the very large doses of atropin which paralyze the muscle substance. Strophanthin (and presumably the other Digitaloid drugs) stimulate in small doses and inhibit in large doses. The effects occur in plexus-free preparations, and hence involve the endings or muscle, presumably the latter. The stimulation is abolished only by the extreme doses of atropin. Physostigmin, Pilocarpin, Muscarin, Cholin and Colchicin produce violent irregular contractions, and also tetanic contraction of plexus-fret- preparations. Their action must be postganglionic; presumably stimula- tion of the vagus endings. The stimulation of these drugs is abolished by small doses of atropin; pilocarpin is antagonized by extremely minute doses; physostigmin requires relatively the largest amount. Atropin. The effects and their localization differ according to con- ditions: Very small doses have no effect on the normal intestine, but remove ' intestinal spasm, due to peripheral vagus stimulation (physostigmin, pilocarpin, etc.; lead colic, anemia of intestine, etc.). The motor response to stimulation of the vagus trunk is lessened, but not abolished. This
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