细胞内胞浆游离钙、血管紧张素Ⅱ和动态血压改变与氨氯地平血药浓度变化的关系

The relationship of changes in plasma amlodipine concentrations with intracellular free calcium,plas ma angiotensin Ⅱand ambulatory blood pressure

目的观察氨氯地平的降压作用与其血浆血药浓度、细胞内胞浆游离钙浓度（[Ca2＋]i）、血管紧张素Ⅱ浓度（[AT－Ⅱ]）和24h动态血压改变的关系。方法给14名原发性高血压病人及性别、年龄严格匹配的正常对照组口服单剂量（5mg）氨氯地平治疗，治疗前后检测上述指标。结果原发性高血压病人之[Ca2＋]i和[AT－Ⅱ]比正常对照组显著升高。口服单剂量氨氯地平治疗后，随着血药浓度上升，血压、[Ca2＋]i和[AT－Ⅱ]显著下降。药物作用的高峰在服药后的6h，且其药物作用可维持24h。治疗后[Ca2＋]i的下降幅度、血药浓度的上升幅度、血压的下降幅度和[AT－Ⅱ]的下降幅度之间有明显的相关性。原发性高血压病人经氨氯地平治疗后，24h平均血压显著下降，降压谷：峰值比率：收缩压力79．27％，舒张压为68．40％。结论以上资料提示：氨氯地平能平稳、有效地降低高血压病人的血压而且其药物作用能维持24h，其降压作用可能通过降低细胞内胞浆游离钙浓度和血管紧张素Ⅱ的浓度而发挥作用。

Objective To evaluate teh relationship of hgutensive effect of amledipine withconcenhahons of plasma ding, intracellular free Calcium ([ca2+]), and Plasma Anatotensin n ([ATn ]) and tory blood pressure (ABP ).Method To detendne aboVe - mentioned prmleters in 14 Patients with essenhal hwrrtension (Inale8, felnal 6, and mean age 58 t 6.2 Yrs. ), with sexand age being well matched tO normotensive groupbefore and after taking alnlodipine 5 mg monodose.[Ca2+ ] i was measured by a Ancrofluormetrie techniqUe using the [ Ca2+ ] i - sensihve probe fura 2/AM. Plasma drug concentration was detendned byGaS Chromatograph -Mass. Results 1. To as compared with contIDI group, the [Ca2+ Ji and [AT-Ⅱ]were markedly increased in the patients. 2. Afteralnlwhpine heabent in hypertensive patientS, theirBP, [Ca2+ ] i and [AT -Ⅱ] were markly decreased, with the increase in plasma anhadipineconcentheion. The Peak effeCt located at 6 hour(plasma alnledipine concendrion was (3.75 t1.91) ng/ml) and continued to 24 hour. 3. Therewere positive correlahons between the ABP andAl[Ca2+ ] i, oh [Ca2+ ] i and the me^ing ednent of plasma amledipine concenhation, andn[Ca2+ ] i and n[AT- H ]' 4. ABP showed.thatin essential hypertensive patientS, the 24 hoursmean BP was reduced from (153.3 i 18.3/92.0 t6.2)rnmHg to (139.4 1 15.8/sa. 6 1 11. 2)~g(P < 0 .01 ) aller amledipine treatment. The calcufatto WP rahos were 79.27% (SBP) aha cd%(DBP). ~ The h^nsive effects ofalnlwhpine therapy mainly was because Of decreasedhoe [Ca2+ ]i and [AT-Ⅱ]. The hyPOtensive effectcan continue for 24 hours.[