摘要:

SUMMARY1. The effect of orally administered ethanol on the vasoconstrictor response of hand resistance vessels to application of ice to the neck has been studied in normal subjects.2. Ethanol significantly reduced the ice response.3. The mechanism of this blocking action is obscure, but a central inhibitory action, possibly at the ponto‐medullary vasomotor centre level, is postulate

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00549.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. After incubation of guinea‐pig atria with3H‐(—)‐noradrenaline, the spontaneous efflux of radioactivity showed two components, an initial rapid efflux with a half life of about 5 min and a slower efflux with a half life greater than 40 min.2. Field stimulation produced an increase in efflux of radioactivity and the force of atrial contractions.3. There was a linear relationship between the spontaneous efflux of radioactivity and the total efflux during periods of stimulation. This was maintained for three periods of stimulation at 30 min intervals. The increase in efflux during stimulation over that in the corresponding resting periods was termed the stimulation‐induced efflux.4. Tetrodotoxin (1.56 μM) markedly reduced the stimulation‐induced efflux and the increase in contractile force in response to stimulation, indicating that these effects were due to excitation of intramural adrenergic nerves. Tetrodotoxin also decreased resting efflux.5. Cocaine (0.1–3 μM) reduced the resting efflux but increased resting contractile force; increases in both stimulation‐induced efflux and positive inotropic response to stimulation were produced. A higher concentration (300 μM) increased resting efflux, decreased stimulation‐induced efflux, and decreased contractile force in resting and stimulation periods.6. Guanethidine in a low concentration (0.1 μM) increased stimulation‐induced efflux and the positive inotropic response to stimulation. A higher concentration (10 μM) markedly increased resting efflux and the resting contractile force; the positive inotropic response to stimulation was only slightly reduced but the'stimulation‐induced efflux was greatly reduced.7. Tyramine (100 μM) increased the resting efflux and initially increased resting contractile force. Tyramine also increased stimulation‐induced efflux; however, it depressed the positive inotropic response to stimulation. These effects of tyramine were much less marked in the presence of cocaine (100 μM).8. Normetanephrine (10 μM) counteracted the effects of cocaine (1 μM) on effluxes and contractile force, but ha

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00550.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Pancreatic secretion has been monitored in the isolated, blood‐perfused canine pancreas, and the effects of depletion of serum calcium by infusion of EGTA on the increases in secretion produced by intra‐arterial injections of dopamine and secretin have been investigated.2. Under resting conditions in preparations in dogs fasted for 24 h, the mean rate of pancreatic secretion was 16.4 μ1/min (s. e. m. = 2,n= 12). The mean concentrations of protein, bicarbonate and chloride in the pancreatic juice were 53.8 mg/ml (s. e. m. = 4.5), 18.0 mmol/1 (s. e. m. = 1.1) and 122.5 mmol/1 (s. e. m. = 7.5), respectively. Infusion of EGTA had no effect on resting secretion.3. Secretion elicited by dopamine or secretin was diminished about 50% during the intra‐arterial infusion of EGTA (10−2mM/ml) in the perfusing blood. The protein concentration in the secretion was diminished to a similar extent. The concentrations of bicarbonate and chloride in the pancreatic juice was not modified by EGTA infusion.4. Concomitant infusion of an equimolar concentration of CaCl2solution abolished the inhibitory effects of EGTA infusion on the secretory responses to dopamine or secretin.5. The results suggest that dopamine and secretin influence the exocrine secretions of the pancreas by actions on both acinar and ductular cells. Acinar cell secretion is more susceptible to depletion of serum calcium levels than is secretion from ductul

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00551.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The biological half‐life of minocycline in serum has been studied in twenty‐one patients and shown to have no relationship to renal function. There is very little excretion of minocycline by the kidney, and practically none is removed by dialysis.2. In normal subjects, minocycline therapy is not accompanied by a significant rise in blood urea concentration or urinary urea excretion. However, high doses may produce a marked increase in urea excretion.3. Of eight patients with impaired renal function who were treated with a normal therapeutic dose of minocycline (200 mg/day), one showed a significant increase in urea excretion and a rise in plasma urea concentration. Two patients with severe unstable renal failure required dialysis following therapy.4. Minocycline is unlikely to accumulate in patients with renal failure due to its predominantly gastrointestinal excretion and is therefore safe to use. However, its protein catabolic effect is dose dependent and if renal function is impaired, even a small increase in urea production may be sufficient to aggravate uraemia. In such patients the normal therapeutic dose (200 mg/day) should not be exceeded and monitoring of renal function is advisa

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00552.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The actions and interactions of compounds with phosphodiesterase‐in‐hibiting activity and of sympathomimetic amines have been studied on contractions of skeletal muscles in chloralose‐anaesthetized cats treated with bethanidine and in which the adrenals were excluded from the circulation.2. Compounds with phosphodiesterase‐inhibiting activity, ICI 63,197, ICI 58,301, papaverine, theophylline, and dipyridamole, potentiated isoprenaline in its depressant effect on tension and fusion of incomplete tetanic contractions of the slow‐contracting soleus muscle, the order of potency being as listed. ICI 63,197 and theophylline also potentiated adrenaline and salbutamol in depressing contractions.3. ICI 63,197 potentiated isoprenaline in its enhancing effect on tension and degree of fusion of incomplete tetanic contractions of the fast‐contracting tibialis anterior and flexor digitorum longus muscles.4. The results are compatible with the hypothesis that the effects of sympathomimetic amines on muscle contractility are mediated by cyclic adenosine‐3',5'‐monophosphate, although this nucleotide and its dibutyryl analogue, injected intra‐arterially, were themselves without any consistent effect.5. High doses of ICI 63,197, ICI 58,301, papaverine and dipyridamole, themselves produced isoprenaline‐like effects on the soleus muscle. These effects were partially antagonized by (±)‐propranolol, (+)‐propranolol, or sotalol. The (+)‐isomer of propranolol was only about ten times less potent than racemic propranolol in this respect. This antagonistic action of propranolol and sotalol appeared to be independent

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00553.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. The effect on plasma renin activity of moderate slow haemorrhage (7.5 ml. kg−1. h−1for 2 h) was studied in intact dogs and in dogs whose adrenals and kidneys had been denervated surgically.2. In dogs with intact renal and adrenal nerves, plasma renin activity rose during haemorrhage without any accompanying change in systemic blood pressure, but with marked decreases in renal function, an increased filtration fraction and an increased haematocrit. The latter effects can be attributed to sympathetic stimulation evoked by haemorrhage.3. In dogs with denervated kidneys and adrenals, haemorrhage did not result in a significant elevation of plasma renin activity until the 2 h collection period, at which time mean systemic blood pressure had fallen 32 mmHg. Renal function changes were less marked and neither filtration fraction nor haematocrit rose, suggesting the absence of sympathetic stimulation.4. It concluded that the sympathetic nervous system plays an important role in the renin response to slow haemorrhage until such time as blood pressure falls sufficiently to activate a second stimulatory mechanism, perhaps a renal baro‐rec

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00554.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Seven β‐adrenoreceptor antagonists, namely (±)‐propranolol, (—)‐propranolol, (±)‐alprenolol, pindolol (prindolol; LB46), practolol, ICI 66082, sotalol and oxprenolol, produced sustained falls in blood pressure and heart rate after intracerebroventricular (icv) administration in conscious, normotensive cats.2. Transient initial rises in blood pressure and heart rate were observed after icv infusions of six of the β‐adrenoreceptor antagonists used, the exception being ICI 66082.3. The isomers (+)‐propranolol and (+)‐alprenolol, which are devoid of β‐adrenoreceptor antagonist activity and the local anaesthetic agents procaine and lignocaine caused initial rises in blood pressure and heart rate, but did not subsequently cause any fall in either blood pressure or heart rate.4. The time of maximum hypotension and bradycardia following icv administration of β‐adrenoreceptor antagonists coincided with the maximum inhibition of the centrally mediated tachycardia in res

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00555.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

SUMMARY1. Administration of levodopa in man and rats resulted in a large increase in the daily excretion in the urine of dopamine and its metabolites, but not of noradrenaline.2. In the rat administration of levodopa substantially increased dopamine concentrations in the heart and brainstem, but noradrenaline concentrations were decreased.3. It is suggested that administration of levodopa leads to dopamine production in concentrations high enough to saturate intraneuronal uptake, so that the main uptake is extraneuronal, hence the major products are dopamine and its metabolites.4. The lack of evidence of increased noradrenaline synthesis in the presence of diminished tissue levels of noradrenaline suggests that either the intraneuronal vesicular uptake or the β‐hydroxylation of dopamine may be an important regulating step in the synthesis of noradrenali

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00556.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1974.tb00557.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY