摘要:

SUMMARY1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in α‐chloralose‐urethane anaesthetized rabbits.2. Intravenous infusion of a 25% glucose solution (0.5 g/kg) over 3 min caused a transient increase in arterial blood pressure and a decrease in renal sympathetic nerve activity. Thereafter, these parameters were restored and remained around preload levels while plasma glucose and insulin concentrations were still elevated.3. Equimolar mannitol solution produced similar patterns of change in blood pressure and nerve activity without an elevation of plasma glucose and insulin levels.4. The transient changes in blood pressure and renal nerve activity could be attributed to acute hypervolaemia indicated by similar changes in plasma osmolality and haematocrits in the two groups of treatment.5. The present study did not support a close relationship between carbohydrate metabolism and the sympathetic nervous system regulating cardiovascular func

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01487.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Standard microelectrode techniques were used to study the effects on the action potential duration (APD) of canine Purkinje fibres of a therapeutic concentration of nine Class I antiarrhythmic drugs. At an extracellular K+ concentration of 5.6 mmol/L all nine agents reduced APD at all drive rates studied (range of interstimulus intervals = 200–1000 ms). At lower levels of K+, quinidine (5 μmol/L) and disopyramide (10 μmol/L) (Class Ia agents) revealed dual effects on APD. At the lowest levels of K+ (2 mmol/L) and the longest interstimulus interval used (2000 ms), both agents significantly prolonged APD. Under all other conditions, APD was either unchanged or reduced. Lignocaine, 15 μmol/L (Class Ib agent) reduced APD at all rates and all K+ concentrations and this effect was greatest at the slowest rates.2. Flecainide (1 μmol/L) (Class Ic) shortened APD at K+= 5.6 and 4 mmol/L but had no effect at K+= 2 mmol/L.3. We conclude that these data result from opposing drug actions on inward sodium and outward potassium currents flowing during the plateau of the action potential.4. Class Ia drugs exhibit significant depression of both currents, with the resultant effect on APD being modulated by external K+ concentration and drive rate.5. Class Ib agents predominantly depress the sodium current and hence shorten APD, and Ic compounds have intermediate actions.6. These differential effects on APD must be considered when planning antiarrhythmic therapy, and are directly relevant to the proarrhythmic propensities of these a

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01488.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The effects of extracellular Na+ concentration ([Na+]o) on serum‐stimulatedc‐fosmRNA induction in vascular smooth muscle cells (VSMC) were studied to examine whether the activation of Na+/H+ exchange and the following intracellular alkalinization are necessary in the induction ofc‐fosin VSMC.2. When monitored with 2′, 7′‐bis (carboxylethyl)‐5(6)‐carboxyfluorescein, the reduction in [Na+]oin HCO3−‐free buffer caused a dose‐dependent inhibition of Na+‐dependent intracellular pH recovery in acid‐loaded VSMC. In addition, serum‐stimulated intracellular alkalinization in VSMC was completely blocked by the removal of extracellular Na+.3. By contrast,c‐fosinduction, quantified by slit blot hybridization ofc‐fosmRNA, was not fully inhibited by the reduction of [Na+]o. Furthermore, amiloride and ethylisopropyl‐amiloride, inhibitors of Na+/H+ exchange, only partially blockedc‐fosinduction by serum.4. We concluded from the observation above, that the intracellular alkalinization caused by the activation of Na+/H+ exchange was unnecessary in serum‐sti

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01489.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2(TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction.2. In 11 OSA drug‐free male patients (age 53 ± 2 years, mean ± s.e.m.; apnoea index 55 ± 15 apnoeas/hour of sleep; body mass index 31 ± 2 kg/m2), we measured the urinary excretion during sleep of 6‐keto‐PGF1‐alpha and of thromboxane TxB2(the stable metabolites of prostacyclin PGI2and of thromboxane A2respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects.3. The urinary ratio of 6‐keto‐PGF1‐alpha to TxB2was significantly (P<0.001) lower in the untreated OSA patients (1.7 ± 0.2) than in the controls (3.1 ± 0.3). It significantly increased with CPAP treatment to 2.3 ± 0.2,P<0.02, which was no longer different from the controls.4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remai

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01490.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. We examined the effects of metoclopramide (MCP: 10 mg i.v.) on plasma atrial natriuretic peptide (ANP) and aldosterone concentrations (PAC) and the effect of ANP on MCP‐induced PAC in four patients with primary glomerular diseases and seven patients with essential hypertension.2. MCP injection caused no significant changes in plasma ANP. MCP produced a marked increase in PAC without a significant change in plasma renin activity.3. The increase in PAC induced by MCP injection was markedly attenuated when preceded by the infusion of ANP (25 ng/kg per min).4. These results suggest that the dopaminergic D2mechanism is not involved in the regulation of ANP secretion and that ANP modulates the dopaminergic regulation of aldosterone secretio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01491.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. Plasma and urine steroid and plasma ACTH levels were measured for 2 weeks in eight subjects (six female, two male) with Cushing's disease with each given 200 mg ketoconazole orally four times daily.2. Treatment was associated with major falls in excretion of free cortisol and the cortisol metabolites tetrahydrocortisol, 5α‐tetrahydrocortisol and tetrahydrocortisone.3. Plasma cortisol and ACTH levels did not change significantly.4. Excretion of the androgen metabolites, androsterone, 11β‐hydroxyandrosterone and aetiocholanolone was also reduced but there was no significant fall in plasma testosterone. Plasma levels of progesterone, 17α‐hydroxyprogesterone and 11β‐deoxycortisol and excretion of pregnanediol, pregnanetriol and tetrahydrodeoxycortisol rose with treatment.5. Analysis of steroid precursor/product ratios indicated that ketoconazole significantly inhibited 11β‐hydroxylase and 17,20‐lyase but not 17α‐hydroxylase in these patients wit

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01492.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice.2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance.3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2‐week period.4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated.5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mic

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01493.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARY1. The present study was undertaken to determine the vasospasmolytic activity of a novel non‐dihydropyridine type of Ca2+channel blocker, SD‐3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts.2. The vasospasmolytic effect of SD‐3211 was investigated using 3,4‐diaminopyridine‐induced rhythmic contraction, in comparison with its enantiomer (SD‐3212), nicardipine and diltiazem. SD‐3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine>SD‐3211>diltiazem>SD‐3212 and being compatible with that for the relaxant effects of these compounds on KCl‐induced contraction in the same specimen.3. Furthermore, the effect of SD‐3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD‐3211 at a concentration of 2 × 10−8mol/L was given for 40 min before and again for 60 min after the ischaemia. SD‐3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post‐ischaemic recovery of developed tension.4. These results suggest that SD‐3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the trea

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1991.tb01494.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY