No abstract

SUMMARY1. In cats anaesthetized with pentobarbitone sodium, atropinized by i.v. atropine methyl nitrate and artificially ventilated, experiments were carried out (a) to localize the site where glycine acts on the ventral surface of the medulla when, on topical application through paired Perspex rings caudal to the trapezoid bodies, it produces a fall in arterial blood pressure, (b) to compare the effects of uni-and bilateral application, and (c) to study the blood pressure effects produced by electrolytic lesions of the glycinesensitive areas.2. Blood pressure fell only a little on unilateral application of glycine through one of the Perspex rings, but a pronounced fall occurred on its bilateral application. The fall was too large to be explained by two minimal responses added together. Thus the application of glycine to one side potentiated the depressor effect of glycine applied to the other side.3. By moving the paired Perspex rings rostrally or caudally to different positions on the medulla and determining for each position the effectiveness of glycine, the glycine-sensitive areas were found to be restricted to a 1.5 mm wide strip situated 1-2 5 mm caudal to the trapezoid bodies. By making electrolytic lesions within the limits of this strip the glycinesensitive areas were found to be not wider than 1-5 mm in the mediolateral direction and to be situated about 4 mm lateral to the mid line. Histologically, such lesions involved the cells of the parvicellular part of the lateral reticular nucleus. 4. Placing an electrode, with a diameter of 1 mm, under light pressure on the glycine-sensitive area produced a short-lasting steep rise in blood

1. In cats anaesthetized with pentobarbitone sodium the effect on arterial blood pressure was examined of substances applied bilaterally to the exposed ventral surface of the brain stem by means of Perspex rings placed lateral to the pyramids and caudal to the trapezoid bodies. Routinely, atropine methyl nitrate, which does not pass the blood—brain barrier, was injected I.V. 2. The cholinomimetic substances carbachol and physostigmine, and the amino acids glycine and GABA, caused a fall in arterial blood pressure. 3. Atropine produced a small but definite rise in arterial blood pressure, antagonized the depressor effects of the cholinomimetic substances, but not those of the amino acids. 4. Strychnine, leptazol and tubocurarine, caused a rise in arterial blood pressure. 5. The depressor and pressor effects are due to changes in vasomotor tone. They are central effects brought about by penetration of the substances into the brain tissue from the ventral surface of the brain stem. They are not due to their absorption into the blood stream. 6. The depressor effects of the cholinomimetic substances may imitate the action of cholinergic neurones, and those of the amino acids that of central inhibitory neurones ending on cells near the ventral surface of the brain stem and exerting an inhibitory influence on vasomotor tone. The pressor effects of strychnine and tubocurarine may in part result from ‘disinhibition’, i.e. from an antagonistic action produced by these drugs on the amino acids released from the central inhibitory neurones.

SUMMARY1. In cats anaesthetized with i.P. pentobarbitone sodium and atropinized with intravenous atropine methyl nitrate, the effects on arterial blood pressure were examined of nicotine, physostigmine, carbachol, glycine and pentobarbitone sodium applied to the exposed ventral surface of the brain stem by means of paired Perspex rings placed across the medulla.The drugs were placed inside each ring in a volume of 10 ,uJ.2. Nicotine (0-5-6 mg/ml.) produced a fall in blood pressure when the upper limit of the areas covered by the rings was about 5-6 mm caudal, but not when it was just caudal to the trapezoid bodies. The depressor effect was obtained both on bilateral and unilateral application. After application the nicotine sensitive area became for several minutes insensitive to its renewed application.3. The depressor effect of nicotine was sensitive to hexamethonium (50 mg/ml.) but resistant to atropine (50 mg/ml.) similarly applied.4. When the nicotine sensitive areas had become insensitive to nicotine, bilateral carotid occlusion produced its normal sustained pressor response.5. By applying the nicotine through a single Perspex ring which could be moved stepwise along and across the medulla, the nicotine sensitive area was localized and the highest sensitivity was found in a region around and a little caudal to the rootlets of the XIIth cranial nerve.6. Physostigmine (25 and 50 mg/ml.) and carbachol (6 mg/ml.) produced a fall in blood pressure when the uppermost limits of the areas covered by the paired rings were 5-6 mm caudal to and also when they were just caudal to the trapezoid bodies. From both regions the effects were obtained on bilateral and unilateral application. Their depressor effects were sensitive to atropine but resistant to hexamethonium similarly applied.

SUMMARY1. In anaesthetized cats under artificial ventilation, a few milligrams of pentobarbitone sodium injected into the cerebral ventricles produced a pronounced fall in arterial blood pressure, which was central in origin and resulted from inhibition of vasomotor tone.2. Pentobarbitone sodium was more effective in lowering blood pressure when injected into the cerebral ventricles than when injected into the cisterna magna, yet the pentobarbitone sodium did not act on structures in the ventricular wall, but acted on structures reached from the subarachnoid space.3. To produce its vasodepressor effect, the pentobarbitone sodium had to pass through the foramina of Luschka into the subarachmoid space beneath the medulla oblongata and to penetrate its ventral surface in a region caudal to the trapezoid bodies and lateral to the pyramids. This was the outcome of experiments in which the pentobarbitone sodium was injected into or perfused through the cerebral ventricles with or without an outflow cannula inserted into the aqueduct or into the fourth ventricle, and of experiments in which pentobarbitone sodium solutions were applied by means of Perspex rings to this region of the exposed ventral surface of the medulla. Whereas the application of pentobarbitone sodium to this region on one side had a weak vasodepressor effect only, its application on both sides produced a pronounced fall in arterial blood pressure.4. The region where pentobarbitone acted on topical application covers the region where nerve cells are found in the marginal glia immediately under the pia mater. The possibility is discussed that these cells are the morphological substrate on which the pentobarbitone acts, that arterial blood pressure is maintained by their activity which is suppressed by the pentobarbitone sodium.