Quarterly journal of experimental physiology (Cambridge, England)最新文献

The aim of this study was to determine whether the degree of stimulation of left ventricular receptors influenced the sensitivity of the carotid sinus baroreceptor reflex. In anaesthetized dogs, the stimulus to left ventricular receptors was changed by changing aortic root and hence ventricular systolic pressure, using a preparation in which the applied pressure did not distend the aortic arch and in which left atrial pressure was controlled. A large step increase in either carotid or left ventricular pressure resulted in vasodilatation both in a perfused hindlimb and in the remainder of the systemic circulation and resulted in a reduction in the response to a change in pressure in the other area. The stimulus-response curves, relating limb and systemic perfusion pressures to small step changes in carotid sinus pressure, were displaced downwards at high left ventricular pressures. However, the curves remained parallel indicating the absence of an interactive effect. These results indicate that the vascular responses to changes in carotid and ventricular pressures show simple additive summation.

Morphology of the carotid body and the ventilatory response to hypoxia were compared in New Zealand genetically hypertensive rats and 'normotensive' control rats from the same genetic stock. Hypertensive rats grew more slowly, had higher blood pressure from 6 weeks of age and developed left ventricular hypertrophy. Carotid bodies of both groups were similar in size but larger than those of a common Wistar strain. Intimal damage and proliferation were seen in 1st- and 2nd-order branches of the carotid body artery in hypertensive rats and point-counting showed that the volume proportion of Type 1 cell nuclei and vascular lumen was reduced and vascular wall increased. In age-matched anaesthetized rats, minute ventilation per 100 g was greater in hypertensives than 'normotensive' when inspiring O2 concentrations of 30, 21, 18, 15, 12, 10 and 8%. However, at each inspired O2 concentration, arterial Pa.O2 was higher and Pa.CO2 lower in hypertensive than in 'normotensive' rats. Hypertensive rats were hyperventilating. The shape of the ventilation/O2 tension curve was similar in hypertensive and 'normotensive' rats; thus carotid body sensitivity to hypoxia was probably unchanged. Possible causes of hyperventilation and the relation of carotid body morphology to hypertension are discussed.

The purpose of this investigation was to examine the metabolism and inactivation of gastrin releasing peptide 10 (GRP10) by endopeptidase-24.11 prepared from the stomach wall. GRP10 was metabolized in vitro by gastric endopeptidase-24.11. The metabolites were purified by high-pressure liquid chromatography and identified as (1-8) GRP10 and (9-10) GRP10 by amino acid analysis, indicating hydrolysis of the His8-Leu9 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRP10 with endopeptidase-24.11 significantly diminished the biological activity of the digests compared to control digests containing heat-inactivated enzyme. This effect was abolished by the enzyme inhibitor phosphoramidon. It is concluded that endopeptidase-24.11 from the stomach metabolizes and inactivates GRP10.

Intracellular pH (pHi) was measured at the tips of extending neurites and in the corresponding cell bodies of single cultured mouse neuroblastoma (N2A) and rat pheochromocytoma cells (PC12) using the fluorescent dye 2,3-di-cyanohydroquinone (DCH). It was observed that pHi at the tip of an extending neurite was consistently 0.2-0.3 pH units higher than pHi in the cell body. Experiments performed on whole cells to establish the types of cellular mechanism which could be responsible for such regional differences demonstrate the presence of Na+-H+ exchange and Cl- HCO3- exchange in these cells. Since regional variations in Ca2i+ have been reported between neurites and the cell body, experiments were performed to examine the possible interactions between pHi and Ca2i+. Intracellular calcium was measured using the fluorescent Ca2+-sensitive dye Indo-1. An increase in pHi, on application of NH4Cl, resulted in a transient elevation of Ca12i+. On subsequent acidification, on removal of NH4Cl, there was a further transient increase in Ca2i+. These changes in Ca2i+ were also present in solutions with low calcium suggesting that Ca2i+ is mobilized from within the cell. The results are discussed in terms of possible mechanisms whereby the extension and retraction of cell processes could be influenced by Ca2i+ and modulated by pHi.

Selective electrical stimulation of the non-myelinated C fibres of the sural nerve in the decerebrated, spinalized rabbit evoked long-latency (76-160 ms), long-lasting (greater than 100 ms) reflex responses in the ipsilateral ankle extensor gastrocnemius medialis (GM). Activation of the same fibres elicited little or no response from the ipsilateral knee flexor semitendinosus (ST). Reflex responses were evoked in both GM and ST muscle nerves by stimulation of the A beta afferents of the sural nerve. The A beta-elicited reflex in GM was enhanced, and that in ST depressed by prior activation of sural nerve C fibres. Strychnine, but not picrotoxin or mecamylamine, blocked C fibre-induced inhibition of the flexor reflex. Pinching the heel with serrated forceps produced an immediate reflex discharge in GM motoneurones, whereas ST responded upon termination of the stimulus. Pinching the second toe evoked reflex activity in ST but not in GM. After strychnine (0.5 mg kg-1), both sets of motoneurones responded simultaneously to stimulation of either the heel or the toe. These data show that sural and other afferent fibres from the heel excite ipsilateral GM motoneurones and inhibit ST reflex responses. One interpretation of these findings is that fine sural afferents activate parallel inhibitory and excitatory pathways, of which the former is sensitive to strychnine and therefore probably mediated by glycine.

Angiotensin II (AII; 300 ng) injected into the lateral cerebral ventricle produced significant drinking responses and also stimulated release of lysine vasopressin (LVP) in conscious, water replete, unrestrained minipigs. Plasma LVP concentration, measured by a specific radioimmunoassay, was decreased by drinking. At the end of the experiment the level was inversely proportional to the volume of water drunk in response to the AII, and not to changes in plasma osmolality. These findings suggest that AII-stimulated LVP release is influenced by a negative feed-back mechanism, probably involving oropharyngeal receptors.

We have used computer simulation of a model neurone and in vitro intracellular recording to demonstrate that the adaptation of repetitive discharge in neocortical neurones can be explained by a fast potassium current whose inactivation is retarded by intracellular calcium. The maximum amplitude of this current determines whether the neurone will discharge in regular or burst mode.

The influence of duodenal infusions of emulsified fat (20% Intralipid) and glucose (40%, w/v) on gastric emptying during the feeding period was studied in five pigs. Gastric emptying was measured by evacuation of gastric contents immediately the pigs had finished feeding in animals fitted with a gastric cannula and a duodenal catheter and fed a solid meal mixed with water. Infusions at various rates of Intralipid and glucose given either from the start of feeding or up to 30 min prior to feeding until the pigs had finished feeding inhibited gastric emptying of dry matter (DM) and liquids in a qualitatively similar but quantitatively different manner. With both infusions the rates of gastric emptying of DM and liquids were progressively reduced with pre-infusions of 0, 10, 20 and 30 min. Slow infusions of Intralipid (2.3 and 4.6 ml/min) inhibited gastric emptying of DM and liquids to a greater extent than equicaloric infusions of glucose (3 and 6 ml/min), but faster infusions of Intralipid (6 ml/min) inhibited emptying less than equicaloric infusions of glucose (8 ml/min). When the DM emptied was converted into digestible energy (DE) there was no evidence that Intralipid inhibited gastric emptying calorically. In contrast the results showed that there was caloric regulation of gastric emptying with infusions of glucose begun at the start of feeding. There was a linear reduction in the rate of DM emptied with increase in the rate of glucose infusion (2-8 ml/min) of 64.5 +/- 4.8 g DM per MJ/min glucose infused, i.e. equivalent to a reduction of 0.98 +/- 0.07 kJ/min DE emptied for each kJ/min glucose infused. These changes in gastric emptying with duodenal infusions of glucose and Intralipid mirror the changes previously observed in food intake following similar infusions, and the results are therefore compatible with control of gastric emptying being an important site of short-term regulation of food intake in the pig.

The effects of prolonged exposure to lowered ambient temperature (18-19 degrees C) for 6 weeks, on thyroid function, were studied in mature female rats. Exposure to cold resulted in a significant rise in serum thyrotrophin level but a fall in serum thyroxine. Radioactive iodine uptake by the thyroid gland was also depressed. Rectal temperature was reduced following cold exposure. Histological examination of the thyroid gland was suggestive of reduced glandular activity. Thus prolonged exposure to lowered ambient temperature leads to a reduction in thyroid gland activity which is accompanied by a lower body temperature.