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[钙拮抗剂与糖调节:尼卡地平对血管张力和胰岛素分泌的不同作用]

[Calcium antagonists and glycoregulation: dissociated effects of nicardipine on vascular tonus and insulin secretion].

作者信息

Marre M, Gauville C, Passa P

出版信息

Arch Mal Coeur Vaiss. 1985 Oct;78(11):1661-6.

PMID:3938238
Abstract

Insulin release is coupled with a calcium entry into the pancreatic B cells. The use of calcium-antagonists may eventually alter glucose homeostasis. To evaluate this possibility, nicardipine action was tested both in vitro and in vivo: 1. on insulin release and vascular resistances from isolated perfused rat pancreases; 2. on 7 hypertensive patients with an established glucose intolerance, during two oral glucose tolerance tests (OGTT) performed successively under placebo and nicardipine (90 mg daily) at a two-week interval. In vitro, the basal insulin release from isolated perfused rat pancreases (86 +/- 15 ng.min-1; n = 27; M +/- SE) was inhibited according to the nicardipine dose by the 5 th min. of infusion: 7.2 +/- 1.5 p.100 of the initial output at 10(-4) M (n = 6; p less than %.001); 33.4 +/- 2.7 p.100 at 10(-6) M (n = 6; p less than 0.001); 87.5 +/- 14.8 p.100 at 10(-8) M (n = 6; ns). The pancreatic vascular resistances declined significantly for the 3 doses, but no dose-response could be registered. In vivo, the mean arterial blood pressure was significantly reduced by nicardipine from 114 +/- 3 mmHg to 95 +/- 3 mmHg (p less than 0.001) without any significant alteration of either glucose tolerance (glycaemias at the 120 th min of OGTT: 9.2 +/- 1.1 mmol.l-1 vs 8.9 +/- 1.2 mmol.-1) or insulin peak: 70 +/- 20 micrograms U.ml-1 vs 67 +/- 22 microU.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

胰岛素释放与钙离子进入胰腺β细胞相偶联。使用钙拮抗剂最终可能会改变葡萄糖稳态。为评估这种可能性,在体外和体内对尼卡地平的作用进行了测试:1. 对分离灌注的大鼠胰腺的胰岛素释放和血管阻力的影响;2. 对7名已确诊糖耐量异常的高血压患者,在间隔两周先后进行的两次口服葡萄糖耐量试验(OGTT)中,先服用安慰剂,后服用尼卡地平(每日90毫克)。在体外,从分离灌注的大鼠胰腺释放的基础胰岛素(86±15纳克·分钟-1;n = 27;平均值±标准误)在输注第5分钟时根据尼卡地平剂量受到抑制:在10(-4)M时为初始输出的7.2±1.5%(n = 6;p<0.001);在10(-6)M时为33.4±2.7%(n = 6;p<0.001);在10(-8)M时为87.5±14.8%(n = 6;无显著差异)。胰腺血管阻力在3个剂量下均显著下降,但未观察到剂量反应关系。在体内,尼卡地平使平均动脉血压从114±3毫米汞柱显著降至95±3毫米汞柱(p<0.001),而葡萄糖耐量(OGTT第120分钟时的血糖:9.2±1.1毫摩尔/升对8.9±1.2毫摩尔/升)或胰岛素峰值(70±20微单位/毫升对67±22微单位/毫升)均无显著改变。(摘要截取自250字)

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