摘要:

Summary—The anticonvulsant effect of compounds that inhibit peptidyl‐dipeptidase (PDP) on bicuculline (BIC)‐ and strychnine (STRYC)‐induced seizures was assessed after intracerebroventricular (ICV) or intraperitoneal (IP) administration in Swiss albino mice. STRYC‐induced seizures were delayed by ICV injections and high IP doses of captopril, but not by ICV or IP injections of enalapril or by lower doses of captopril (0.1 mg/kg and 1 mg/kg IP). BIC‐induced seizures were not suppressed by ICV or IP injections of either compound; on the contrary, captopril and enalapril exhibited proconvulsant effects when given IP or ICV by shortening the time of onset of tonic seizures and death. Results indicate that the anticonvulsant effect of captopril against STRYC‐induced seizures is not mediated by central γ‐aminobutyric acid (GABA) receptors or by the i

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00547.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 μg/kg IV; diltiazem 300 μg/kg IV; nifedipine 5 μg/kg IV; nicardipine 50 μg/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino‐aortic denervation (SAD).In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective.SAD caused a 2–2.5‐fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate.This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs i

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00548.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Microelectrodes were used to study the comparative effects of 2 calcium channel blockers on glucose‐induced electrical activity in mouse beta cells. In 2.8 mM glucose, verapamil (10−5M), but not nifedipine (10−7M), induces a silent depolarization. In 11.1 mM glucose, verapamil (10−7to 5.10−5M) induces continuous spike activity by a decrease in the maximum repolarization potential. Nifedipine (10−10to 10−6M) induces the same activity, but subsequent to a hyperpolarization of the cell at the maximal repolarization potential followed by a silent phase to the plateau potential. The 2 drugs induce a dose‐dependent decrease in spike frequency without any change in spike amplitude. In 22 mM glucose exposure to nifedipine, but not to verapamil, induces a transient period of slow‐wave activity. The 2 drugs induce a dose‐dependent decrease in spike frequency. At higher concentrations (nifedipine>10−7M; verapamil>10−6M) they induce the disappearance of spikes through a decrease in amplitude. These results show that the beta cell is more sensitive to nifedipine (ED50= 3 times 10−8M) than to verapamil, and that glucose stimulation increases the cell's sensitivity to verapamil (11.1 mM glucose: ED50= 10−5M versus 5times10−7M in 22 mM

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00549.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The aim of this work was to study the influence of beta‐adrenoreceptor blockade on the adaptation to exercise of one of the hormonal systems (arginine vasopressin) involved in the regulation of blood volume and pressure in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) was measured in SHR and WKY rats during 11 wk of swim training. At the end of the training program we determined post‐exercise values of plasma arginine‐vasopressin (pAVP), osmolality (pOsm), K+ (pK+), Na+ (pNa+), hemoglobin (Hgb), and hematocrit (Hct) in SHR and WKY rats. The following groups were studied: control (C), propranolol treated (PC), swim trained (S), and propranolol‐treated and swim‐trained (PS). SBP was significantly reduced by swim training or propranolol, bu these beneficial effects on SBP were attenuated when propranolol and swim training were combined. pNa+ and pOsm were significantly reduced by training alone in SHR. This reduction of pNa+ and, consequently, of pOsmol without any modification of other parameters could suggest an Na+ loss. In contrast, the SHR group treated with propranolol alone showed a significant reduction in Hct, suggesting an increased plasma volume without Na+ loss.PS SHR showed a significant reduction of Hgb, Hct, proteins, pNa+, and pOsmol, probably as a consequence of the additive effects of swimming‐ and propranolol‐induced hypervolemia with Na+ loss. The slight and nonsignificant reduction in pAVP observed with either training or propranolol treatment alone became much more pronounced and statistically significant when the 2 treatments were combined. WKY rats showed a much smaller response to exercise and beta‐adrenoreceptor blockade than SHR.We conclude that the hypervolemia suggested in PS SHR could be a possible cause of attenuation of the beneficial effects of either swimming or p

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00550.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Cell Na+ and Ca2+concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+‐countertransport system. Cytosolic free Ca2+concentration is also controlled by the Na+–H+ exchange activity. To analyze the changes in cytosolic Ca2+concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]iwas increased in platelets from 169±30 to 321±61 nmol/l (n= 7,P<0.02) and unchanged in erythrocytes (121±6 and 104±7 nmol/l). This increase in platelet [Ca2+]iwas not accompanied by a change in serotonin content (5.43±0.67vs5.49±0.61 10−7mol per 1011cells) and could not be reproduced byin vitroaddition of 10−4mol/l ouabain (198±33vs186±73 nmol/l). The enhanced [Ca2+]iin platelets is thus not a short‐term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+stores or an enhancedin vivostimulation by hormones o

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00551.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Blood pressure, heart rate, oxygen consumption, plasma concentrations of catecholamines, renin, aldosterone and lactate were measured in 6 normotensive volunteers during a randomized crossover study of oral ketanserin (20 mg × 7) and placebo; measurements were made at rest and during maximal dynamic exercise on a bicycle ergometer. At rest ketanserin reduced blood pressure without modifying heart rate or plasma noradrelanine and adrenaline. Duration of exercise and blood lactate levels did not differ between the ketanserin and the control group. During exercise only systolic blood pressure was significantly decreased on ketanserin at maximal work rate whereas heart rate did not change. Plasma noradrenaline was significantly increased and plasma aldosterone significantly decreased during exercise in ketanserin‐treated subjects whereas plasma renin activity and plasma adrenaline remained unchanged. Finally, under ketanserin oxygen concumption during exercise was reduced. The results suggest that ketanserin might interfere with the sympathetic nervous system and aldosterone secretion in

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00552.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—This study evaluated the effects of acute doses of zopiclone (7.5 mg), triazolam (0.25 mg) and placebo on memory and psychomotor performance of 12 normal volunteers.The subjects received both drugs in a repeated measure, double‐blind Latin square design. The tests (CFF, CRT, DSST, memory assessments) were performed before and 2 and 6 hr after treatment. Zopiclone and triazolam induced an anterograde amnesia affecting short‐term and long‐term memory which lasted less than 6 hr. No retrograde amnesia was observed. Two hr after drug intake of both hypnotics psychomotor performances were significantly altered compared with placebo. The subjects also felt more drowsy, dizzy, clumsy and tired, and less alert and energetic 2 hr after zopiclone and triazolam compared to placebo. There was no difference between the effects of the two hypnotics at the doses

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00553.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY