NIFEDIPINE BLOCKS ACTH AND CORTISOL RELEASE IN MAN

1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.     

硝苯吡啶舌下含服治疗高血压病40例观察

采用舌下含服硝苯吡啶治疗Ⅰ期～Ⅱ期高血压病门诊病例40例,服药30min后,血压下降1.3kPa～2.0kpa5例,下降2.1kpa～2.6kPa22例,下降2.8kPa～3.7kPa13例,用药前平均血压24.4/13.5kPa,用药后平均血压21.8/12.8kPa,降压迅速可靠,未发现明显副作用。     

硝苯毗啶及山莨菪碱对大鼠血小板膜流动性及血小板聚集功能的影响

硝苯吡啶与山莨菪碱分别可使大鼠血小板膜微粘度最大增加38.3％及37.1％.并使大鼠血小板5min最大聚集率降低40.5％及42.0％(P值皆小于0.001)。药物效应随其浓度增加而增强,当药物浓度达最大药物效应时,再增加浓度反而使其药物效应减弱。两种药物的血小板膜作用曲线及其抑制血小板聚集作用曲线基本相似。     

Effects of the calcium antagonist, isradipine, and nifedipine on resting and exercise haemodynamics and the neurohumoral system in patients with stable chronic angina

In a randomized double-blind study, the haemodynamic and anti-ischaemic effects of the new dihydropyridine calcium channel blocker isradipine (5 mg and 10 mg thrice daily (t.i.d.) were investigated over 1 week in nine patients with coronary artery disease and chronic effort angina and compared with nifedipine (20 mg t.i.d.) and placebo. In standardized exercise stress tests and exercise radionuclide ventriculography, haemodynamics improved under medication compared with placebo: resting end-diastolic and end-systolic volume index decreased on isradipine 5 mg, 10 mg and on nifedipine, and ejection fraction at rest increased with all medications. Resting mean arterial pressure was reduced compared with placebo accompanied by a decrease in systemic vascular resistance (P less than 0.05) and systolic wall tension (P less than 0.05). Cumulative ST-segment depression was significantly reduced by all three medications (-48%, -23%, -36%), while the increase in work capacity was insignificant. No significant change was found for either heart rate, double product, cardiac index, or stroke work index. Resting plasma levels of noradrenaline, adrenaline and renin activity increased with all three medications (except adrenaline at isradipine 5 mg). Isradipine has favourable effects comparable with those of nifedipine in patients with chronic stable angina and can be safely administered in these patients.     

尼群地平(NT)和硝苯吡啶(NF)对离体豚鼠工作心脏的作用

连续记录的豚鼠离体工作心脏100min,50min内各项指标(AF、CF、LVP、dp/dtmax、ASP和HR等)值较稳定和可靠。其后有自然衰竭趋势,-dp/dtmax最先减慢,提示心脏的自然衰竭与心室舒张功能受损有关。0.1-100nMN T和0.001—10nM有负性肌力和降低心泵的作用,且呈剂量依赖关系。NT和NF抑制AF的ID_(50),分别为15.2nM和1.03nM;+dp/dtmax的ID_(50),分别为52.4nM和3.3nM;-dp/dtmax的ID_(50),分别为56.3nM和1.6nM,两者相差15倍以上,差异显著,提示NT对心脏的抑制作用比NF弱得多。     

硝苯啶光解反应的研究

硝苯啶对光不稳定。在漫射光和钨灯光下其甲醇溶液的光解为表观一级反应,并受各种因素影响。本文报道波长、受光强度和浓度对光解的影响。在漫射光下表观速度常数为灯光下的1.6倍,而初始浓度降低可使反应速度常数扩大。     

Absence of anxiolytic effects of calcium channel antagonists

The potential anxiolytic effects of some calcium channel antagonists (nifedipine, nicardipine, and ±verapamil) were investigated in the elevated plus-maze test in mice. The acute effects of the above-mentioned drugs were compared with those of phenobarbitone and ±propanolol. Results showed that control mice spent less time in the open than in the closed arms, reflecting increased anxiety. Both phenobarbitone (20 mg/kg i.p.) and ±propanolol (5 mg/kg i.p.) increased the percentage of entries into open arms as well as the time spent on the open arms. Nifedipine (2 and 4 mg/kg i.p.), nicardipine (0.5 and 1.0 mg/kg i.p.), and ±verapamil (5 and 10 mg/kg i.p.) failed to alter significantly the behavior of mice. In summary, although there have been some reports based on other tests that calcium antagonists may have potential anxiolytic properties, this conclusion has not been supported by our results from the elevated plus-maze test.     

CARDIOVASCULAR RESPONSES TO NIFEDIPINE IN ANAESTHETIZED RATS WITH ABNORMAL BLOOD GAS/PH LEVELS

1. Blood pressure and pulse rate responses to intravenously (i.v.) administered nifedipine were studied in chloralose-anaesthetized rats subjected to hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis, or hypercarbia with acidosis. 2. Ventilation with a gas mixture of 17% O2, 28% O2, or 23% O2 with 5% CO2 at a fixed stroke volume (10 mL/kg) and rate (80 strokes/min) induced hypoxaemia, hyperoxaemia or hypercarbia, respectively. Hypocarbia was induced by ventilation with 17% O2 at 160 strokes/min. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3, respectively, in animals ventilated with room air. 3. There were significant decreases in blood pressure and pulse rate during acidosis, and increases in pulse rate during alkalosis and hypercarbia. No marked changes in these parameters were observed under the other experimental conditions. 4. The control animals showed a dose-dependent decrease in blood pressure without marked changes in pulse rate in response to nifedipine injection. 5. Significant reductions in the hypotensive effect of nifedipine were observed in rats subjected to alkalosis, acidosis, or hypercarbia. A similar tendency was also found during hypocarbia while the responses to nifedipine during hypoxaemia and hyperoxaemia were statistically the same as those in the controls. 6. It is concluded that alterations of blood pH reduce the hypotensive effect of nifedipine, and we suggest that blood pH changes probably play a more important role than PO2 or PCO2 abnormalities in altering the cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats.