Biomedical subjects
Publications and source records attributed to J R Oliver.
Chronic (2 weeks) guanethidine treatment of rabbits depleted left ventricular noradrenaline and increased sarcolemmal beta-receptor density and protein yield. Total adenylyl cyclase activity was unchanged. Chronic sinoaortic denervation did not affect ventricular catecholamines and only marginally reduced beta-receptor numbers.
During the first 20 days postpartum of the rat, a period of rapid muscle growth, resting potentials and maximum rate of rise and overshoot of action potentials recorded from fast and slow twitch muscle fibres all increased, although did not reach adult values. The action potential of fast twitch muscle fibres had a greater maximum rate of rise and overshoot than that of slow twitch muscle fibres of the same age. Innervation had a marked influence upon maintenance of the electrical properties of muscle fibres in the neonate since denervation reduced the value of the resting potential and maximum rate of rise and overshoot of the action potential. Neverthless, some differences between action potentials recorded from the two fibre types remained 4 days after denervation.
Acute effects of 6-hydroxydopamine (6-OHDA, 400--900 microgram kg-1 intracisternally, i.c.i.) consisted of bradycardia and hypertension, maximal 2--3 h after injection and preceded after some doses by a phase of hypotension. This pattern was obtained in completely conscious rabbits and after propanidid and sodium pentobarbitone anesthesia. After 600 microgram kg-1 i.c.i. 6-OHDA the peak rise in blood pressure (25 +/- 3.8 mm Hg) was due to a rise in peripheral resistance involving particularly renal and intestinal beds. Suprapontine mechanisms contributed to both hypertension and bradycardia. Giving pontine rabbits 6-OHDA elicited a short-latency fall in blood pressure, resembling the hypotensive phase in intact animals. Chronic effects 7 days after 600 microgram kg-1 included a rapid loss of 10% of body weight associated with reduction in food and water intake. To avoid secondary circulatory effects the rabbits were artificially fed, halving the weight loss. At 7 days blood pressure had fallen by 7.4 +/- 2.3 mm Hg probably owing to this residual weight loss. From experiments involving administration of phenotolamine and clonidine in intact rabbits and the responses of pontine animals it is likely that both descending and ascending catecholaminergic pathways have inhibitory effects on blood pressure, though some of the pathways may also be excitatory. Absence of specific chronic circulatory changes may be due to compensation through parallel pathways involving other transmitters.
The carotid bodies were stimulated in the anesthetized pig-tailed macaque monkey (Macaca nemestrina) using i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. In spontaneously breathing animals, brief stimulations of the chemoreceptors consistently caused an increase in pulmonary ventilation, bradycardia, and an increase in femoral vascular resistance. When the same chemoreceptor stimulus was superimposed during the apneic period, reflexly evoked by stimulating either the central ends of the superior laryngeal nerves or the nasopharynx, the respiratory stimulation was absent or minimal, but the bradycardia and vasconstriction were greatly enhanced and exceeded the summed responses of separate stimulation of the chemoreceptors and one or the other of the upper-airways inputs. With sustained stimulation of the carotid bodies, hyperventilation, tachycardia, and femoral vasodilatation occurred due to overriding respiratory mechanisms. When superior laryngeal nerve stimulation was superimposed on this response, apnea occurred and tachycardia was reversed to bradycardia, and femoral vascular resistance increased above resting level. The interaction of autonomic responses resulting from chemoreceptor stimulation and from increases in the upper-airways inputs are qualitatively similar in the monkey and in subprimate species. Those involving specifically cardioinhibitory vagal responses are, in part at least, dependent on mechanisms related to the concomitant changes in respiration.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Glucagon secretion and its control have been studied in perifused isolated islets of Langerhans of the rat. It was shown that a low concentration of glucose per se does not cause increased glucagon secretion, but that at low glucose concentrations the amino acid arginine stimulates a biphasic secretory response. Such amino acid stimulated glucagon secretion can be suppressed by increasing the glucose content of the perifused media from 1.67 to 5.5 or 16.7 mM; insulin secretion is also then increased. Since high concentrations of added porcine insulin (10 mU/ml) did not affect amino acid stimulated glucagon secretion at low glucose concentration, it was concluded that high concentrations of glucose and not insulin secreted in response to that glucose are probably responsible for suppression of glucagon secretion. At low concentrations of glucose, epinephrine (2.5 X 10(-7) M) also stimulated glucagon secretion. It is concluded that isolated rat islets of Langerhans can be used for the study of glucagon secretion in vitro, and that substances appearing in the blood in vivo at low glucose concentrations are probably responsible for increased glucagon secretion under conditions associated with hypoglycemia.
1. The haemodynamic changes during the development of hypertension in rabbits have been studied for 1 week before and 4-5 weeks after sham-operation (thirteen rabbits) or bilateral renal cellophan wrapping (thirteen rabbits), Doppler flowmeters being used to measure cardiac output. 2. There was a significant but transient rise in cardiac output on post-operative day 4 in six of thirteen sham-operated rabbits and six of thirteen renal-wrap rabbits before development of hypertension. Both groups showed the same rise in mean cardiac output of 10%. The reise in cardiac output was more transient than in other species, and was not essential for subsequent development of hypertension.
Serial measurements of cardiac output (CO), mean arterial pressure (MAP), heart rate, and total peripheral resistance (TPR), were made on unanesthetized rabbits with previously implanted Doppler flowmeters. After 2 days of control measurements the rabbits were subjected alternatively to bilateral renal cellophane wrapping (wrap group) or to sham operation and additional measurements were made 1, 2, 4, 8, 16, 25, and 32 days after operation. During the 1st week after operation changes in CO were identical in the wrap and sham-operated groups, with an overall increase to a value of 110% of control on day 4 (P less than 0.05). Thereafter CO fell gradually, reaching 75% of control by day 32 in the wrap group, but only 95% of control in the sham-operated group. When CO was expressed per unit of body weight the latter differences were somewhat reduced, but still were significant. In wrap animals MAP and TPR rose progressively to 155% and 194% of control by day 32. In the sham-operated group the corresponding increases to 108% and 118% of control were significantly smaller. The MAP and TPR of the renal wrap rabbits exceeded the values in sham-operated rabbits, even over the 1st week after operation, by an average for MAP of 8.6 +/- 1.4% (P less than 0.001), and for TPR of 8.0 +/- 2.5% (P = 0.01). The results suggest that the changes in CO during the 1st week were a nonspecific consequence of the preceding wrap or sham operation. They bore no apparent relationship to the subsequent development of the hypertension which was "resistance-mediated" from the earliest stages. We conclude that the present findings for the rabbit differ from those reported for other species and do not conform to the changes predicted by the autoregulation theory of the pathogenesis of hypertension.
Somatostatin (1 mug/ml) inhibited glucose (16.7 mM)-stimulated 45Ca uptake by isolated rat islets incubated in media containing no added calcium or calcium at a low concentration (0.2mM). Epinephrine (50 mug/ml) and mannoheptulose (20mM) also inhibited 45Ca uptake by islets incubated in the presence of calcium (0.2mM). Addition of glucose (16.7 mM) caused a small but significant increase in insulin release from islets incubated in media containing no added calcium. In the presence of a low concentration of calcium (0.2 mM), glucose caused a much greater increase in insulin secretion which was inhibited by addition of somatostatin, epinephrine or mannoheptulose.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Groups of normal rats and of normal and insulin-immunized guinea pigs were injected intravasculary with mixtures of radio-iodinated and unlabelled porcine insulins. No differences could be discerned between the fates of radio-iodinated and unlabelled insulins in normal or immune guinea pigs except with respect to the kidneys of normal animals, which seemed to accumlate TCA-precipitable radioactive substances devoid of immunoreactivity. The abnormally slow disappearance of insulin from the plasma and its persistent accumulation in the livers and spleens of immune guinea pigs were not affected by prior treatment for three days with large daily doses (ca 20 mg/kg body wt.) of hydrocortisone acetate.
Explore the source record for details and available documents.
Changes in mean arterial pressure (M.A.P.) have been produced in conscious rabbits by inflation of balloon cuffs previously implanted round the inferior vena cave and aorta; Sigmoid stimulus/response curves (M.A.P./Heart Period, H.P.) were constructed. Clonidine caused a striking dose dependent increase in gain of the reflex arc in both normal rabbits and rabbits with renal hypertension. The largest effect was upon vagal motorneurones but a similar but smaller effect was present in vagotomised animals. Similar changes in the baro-reflex arc were produced by injection of very much smaller doses of clonidine into the lateral cerebral ventricle. Recordings made from single aortic baroreceptor fibres in anaesthetised rabbits showed again a dose dependeent sensitisation. These results suggest that the bradycardia caused by clonidine is largely mediated via an action in the brain on the baroreflex arc, with an additional action on the baroreceptors themselves. Preliminary results in normal man show a similar increase in the gain of this reflex after intravenous clonidine (150 mug).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.