ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb03010.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02991.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1The arterial baroreceptors are reset to operate at higher pressure levels in hypertension. Rapid (acute) resetting occurs within the first few minutes after elevation of arterial pressure, but is only partial because the increased threshold for baroreceptor activation represents only 25‐50% of the arterial pressure increase.2Complete resetting occurs when the increase in pressure threshold equals the increase in arterial pressure; in the rat this is present after 48 h hypertension.3The aortic calibre was studied in freely moving rats; the time taken for the diastolic calibre to reach maximum dilation correlated with the time taken for complete resetting of the threshold of the aortic baroreceptors. During transient pressure increases the displacement of the diastolic calibre was much greater than the increase in pulsation, indicating that, under physiological conditions, sustained distension of the diastolic calibre is an important factor in aortic baroreceptor distortion.4The relative change of the diastolic calibre, in relation to control calibre, remains relatively constant during transient pressure changes in aortae of increased calibre produced by chronic hypertension or growth.5It is concluded that complete resetting of the baroreceptors in hypertension occurs when the increased stress on the arterial wall is matched by a proportional increase in diastolic calibr

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02992.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The effects of some drugs acting at the central‐type benzodiazepines receptors on blood glucose levels in mice were studied.2. Clonazepam, injected intraperitoneally in doses of 0.625–5 mg, produced a dose‐dependent increase in blood glucose 30 min after administration.3. The hyperglycaemic effect of clonazepam (2.5 mg/kg, i.p.) was dose‐dependently reduced by Ro 15–1788 (10–40 mg/kg, i.v.), a benzodiazepine antagonist.4. Ro 5–3663, a GABA antagonist which may act at the picrotoxinin site, produced a significant increase in blood glucose (5 or 10 mg/kg, i.p.); however, when given together with clonazepam (2.5 mg/kg, i.p.) attenuation of the hyperglycaemic effect was observed.5. Pk 8165, a partial agonist, lacked an effect on blood glucose over the dose range of 5–20 mg/kg, i.p. but caused a slight increase in blood glucose in a dose o

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01902.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls.2. In the GHR, the mean BP in the BRC‐treated group over the 13 day period of study was significantly lower than in the vehicle‐treated group. In the NT rats, the mean BP in the BRC‐treated group over the 13 day period was also significantly lower than in the vehicle‐treated group.3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC‐treated group than in the vehicle‐treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC‐treated group was, however, not significantly different from that in the vehicle‐treated group.4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC‐treated GHR than in the BRC‐treated NT rats compared with their respective vehicle‐treated groups.5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hy

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01903.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1Pressure threshold (Pth) and suprathreshold pressure sensitivity (Sth) are important measures of the pressure‐discharge characteristics of arterial baroreceptors. Anin vitropreparation of the rat aortic arch‐aortic nerve has been used to assess the influence of extracellular ion concentration, distensibility, smooth muscle activation and rapid resetting on single fibre baroreceptor discharge.2Changes in extracellular cations alter Pth and Sth in a reciprocal manner, suggesting that these two properties share common excitatory mechanisms probably at the level of membrane ion conductance channels.3During normal development and ageing in normotensive rats, Pth and blood pressure are fairly constant even during periods of greatly changing aortic distensibility. Sth increases progressively to maturity and then decreases somewhat with advanced age.4During hypertension, changes in distensibility in spontaneously hypertensive rats do not account for changes in Pth and Sth.5The capacity of arterial baroreceptors to rapidly reset during acute changes in the conditioning mean arterial pressure is not altered by chronic resetting, decreases in distensibility or by differences in the initial Pth or Sth of individual baroreceptors.6Within the maximal physiological or pathophysiological range, the prevailing or conditioning mean arterial pressure appears to be the most potent modulator of arterial baroreceptor discha

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02993.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Perhexilene, a long‐acting anti‐anginal drug, can induce adverse effects on the liver which may be dose‐dependent. At high concentrations, perhexilene causes marked morphological change in hepatocyte lysosomes. The current study examined the effect of ‘therapeutic’ doses of perhexilene on hepatic lysosomal function, particularly the biliary release of lysosomal enzymes, using an isolated perfused rat liver (IPRL) model.2. Pharmacokinetic studies demonstrated that clearance of single doses of perhexilene by the perfused rat liver was dose‐dependent and established a ‘therapeutic’ dose of 0.6 mg using the IPRL. A 5 day pretreatment regimen of 20 mg/kg per day was shown to produce ‘therapeutic’ perhexilene concentrations of 150–210 ng/ml.3. At perhexilene concentrations equating the ‘therapeutic’ range in man, the major effect of perhexilene was at the biliary pole of the hepatocyte. In 5 day pretreatment dose studies, lysosomal enzyme excretion into bile was markedly increased. In single dose studies, the increase in biliary lysosomal enzyme output partially reflected an increase in bile water production which was not seen with the 5 day pretreatment regimen. Hepatic and perfusate lysosomal enzyme activities were not affected.4. This selective effect of perhexilene on hepatocyte‐to‐bile lysosomal excretion may reflect intracellula

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01905.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1A change in the arterial pressure‐sympathetic activity or heart rate relation (baroreflex resetting) can result from resetting of baroreceptors (‘peripheral’resetting) or from an altered coupling within the central nervous system of afferent baroreceptor to efferent nerve activities (‘central’resetting).2.‘Peripheral’resetting involves a shift in the pressure‐baroreceptor activity curve in the direction of the prevailing level of arterial pressure, e.g. after elevations in pressure, the baroreceptor pressure threshold (Pth) is increased and activity reduced at equivalent pressures and vascular strains.3.‘Peripheral’resetting occurs during the diastolic phase of a cardiac cycle (instantaneous resetting), after brief exposure to elevated pressure (acute resetting), and during chronic hypertension or when chronic structural changes in the vasculature have occurred (chronic resetting).4Mechanisms include: (i) changes in the mechanical properties of the vessel wall that may alter the tension on the receptors; (ii) ionic mechanisms operating at the neuronal membrane such as activation of Na+, K+‐ATPase; and (iii) release of endothelial factors that may modulate baroreceptor sensitivity.5Acute resetting of baroreceptors can be prevented or attenuated when the sustained elevations in pressure are pulsatile rather than static. Increases in flow increase carotid sinus nerve activity at constant pressure and strain and decrease the Pth of baroreceptors.6.‘Central’resetting can involve neural‐humoral interactions or an altered responsiveness of central neurons mediating the baroreflex to changes in afferent baroreceptor activity.7During static pressure, the continuous baroreceptor discharge causes significant‘central’resetting, i.e. sympathetic activity escapes from baroreflex inhibition. In contrast, during pulsatile pressure, the pulse phasic baroreceptor discharge minimizes‘central’resetting causi

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb02994.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. Both dietary magnesium depletion and potassium depletion (confirmed by tissue analysis) were induced in rats which were then compared with rats treated with chlorothiazide (250 mg/kg diet) and rats on a control synthetic diet.2. Brain and muscle intracellular pH was measured by using a surface coil and [31P]‐NMR to measure the chemical shift of inorganic phosphate. pH was also measured in isolated perfused hearts from control and magnesium‐deficient rats. Intracellular magnesium status was assessed by measuring the chemical shift of β‐ATP in brain.3. There was no evidence for magnesium deficiency in the chlorothiazide‐treated rats on tissue analysis or on chemical shift of β‐ATP in brain. Both magnesium and potassium deficiency, but not chlorothiazide treatment, were associated with an extracellular alkalosis.4. Magnesium deficiency led to an intracellular alkalosis in brain, muscle and heart. Chlorothiazide treatment led to an alkalosis in brain. Potassium deficiency was associated with a normal intracellular pH in brain and muscle.5. Magnesium depletion and chlorothiazide treatment produce intracellular alkalosis by unknown m

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01906.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

SUMMARY1. The effects of taurine on cardiac inotropic state and relaxation were studied in the isolated rabbit heart using solutions containing three concentrations of calcium: 0.7, 1.8 and 3.0 mmol/l.2. Increases in Ca2+caused increases in inotropic indices, but had no effect on rate constant of relaxation.3. Taurine had a positive inotropic effect at Ca2+= 0.7 mmol/l, an equivocal effect at Ca2+= 1.8 mmol/l and a negative inotropic effect at Ca2+= 3.0 mmol/l.4. Taurine had no effect on the rate constant of relaxation at any Ca2+concentration.5. Taurine modulates the positive inotropic effect of Ca2+but neither taurine nor Ca2+affect the rate constant of relaxation.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1989.tb01907.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY