Alam S, Purdie D M, Johnson A G
Queensland University Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Australia.
J Hypertens. 1999 Aug;17(8):1195-202. doi: 10.1097/00004872-199917080-00020.
To evaluate whether prostaglandin inhibition with the non-steroidal anti-inflammatory drug (NSAID), indomethacin (I) interacts synergistically with different doses of salt (NaCl) in elevating systolic blood pressure (SBP).
This randomized, placebo-controlled, double-blind, crossover study examined the interaction between NaCl and the prostaglandin inhibitor, I in 31 healthy elderly individuals with a mean age (+/- SD) of 68.7+/-5.7 years (range 61-85 years). Participants aged more than 60 years on a 140 mmol/day NaCl dose for 6 weeks were chosen with normal blood pressure [24-h SBP <148 mm Hg, diastolic blood pressure (DBP) <85 mm Hg on the Takeda Ambulatory Blood Pressure Monitor (TABPM); n = 15] and isolated systolic hypertension (ISH), [24-h SBP >148 mm Hg, 24-h DBP <85 mm Hg on TABPM; n = 16]. Exclusion criteria included uncontrolled hypertension (SBP >220 mm Hg and/or DBP >110 mm Hg), cardiac disease, creatinine clearance <60 ml/min, dementia and recent cerebrovascular accident or secondary hypertension. A 2x2 Latin square design was structured using four treatment groups [low salt (NaCl = 90 mmol/day) + I placebo, high salt (NaCl = 240 mmol/day) + I placebo, low salt + I (25 mg three times daily) and high salt + I] for 2 weeks each, balanced and interspersed with 2 week washout periods to minimize carryover effects. Twenty-four hour SBP, DBP and heart rate were measured and summarized using a moving interval averaging technique. The mean change in 24-h SBP, DBP, heart rate, urinary Na+, K+, protein and creatinine, creatinine clearance and serum electrolytes were compared across treatments in the total cohort and in ISH and control groups separately using ANCOVA (SAS).
In the total cohort, compared with low NaCl, chronic high NaCl increased mean SBP (5.76 mm Hg; P = 0.0002) and DBP (3.36 mm Hg; P = 0.002). Indomethacin significantly increased mean SBP (2.66 mm Hg, P = 0.015) but not DBP (0.31 mm Hg, P = 0.419). High salt and I were additive (SBPT, DBPT) but there was no interaction (P = 0.795 and P = 0.739, respectively). Additionally, chronic high NaCl increased serum Na (P = 0.0001) and 24-h urinary Na (P = 0.0001) as expected. Indomethacin significantly decreased mean heart rate (P = 0.018). The effects of NaCl and I on SBP, DBP and heart rate were not modified by age, alcohol intake, serum K+, body mass index or treatment order. In the ISH group, NaCl dose significantly elevated SBP (9.87 mm Hg; P = 0.0001) and DBP (5.26 mm Hg, P = 0.006) but did not significantly alter blood pressure in the normotensive group. Indomethacin significantly elevated SBP (P = 0.03) in normotensive individuals but had no effect on blood pressure in the ISH group.
Chronic high salt diet elevated blood pressure more than I in the total cohort of elderly individuals. No interaction was demonstrated and their effects were additive. In the ISH group, chronic high salt diet significantly increased SBP and DBP while I failed to alter blood pressure. In the normotensive group, I, but not salt, elevated SBP. Patients with ISH are sensitive to the pressor effect of NaCl but resistant to the pressor effect of prostaglandin inhibition in contrast to elderly normotensive control individuals where the reverse was found.
评估使用非甾体抗炎药（NSAID）吲哚美辛（I）抑制前列腺素与不同剂量的盐（氯化钠）在升高收缩压（SBP）方面是否存在协同作用。
这项随机、安慰剂对照、双盲、交叉研究，在31名平均年龄（±标准差）为68.7±5.7岁（范围61 - 85岁）的健康老年人中，研究了氯化钠与前列腺素抑制剂I之间的相互作用。选择年龄超过60岁、每日氯化钠摄入量为140 mmol，持续6周且血压正常的参与者[使用武田动态血压监测仪（TABPM）测量24小时收缩压<148 mmHg，舒张压（DBP）<85 mmHg；n = 15]以及单纯收缩期高血压患者[使用TABPM测量24小时收缩压>148 mmHg，24小时舒张压<85 mmHg；n = 16]。排除标准包括未控制的高血压（收缩压>220 mmHg和/或舒张压>110 mmHg）、心脏病、肌酐清除率<60 ml/min、痴呆以及近期脑血管意外或继发性高血压。采用2×2拉丁方设计，分为四个治疗组[低盐（氯化钠 = 90 mmol/天）+ I安慰剂、高盐（氯化钠 = 240 mmol/天）+ I安慰剂、低盐 + I（每日三次，每次25 mg）和高盐 + I]，每组治疗2周，期间穿插2周的洗脱期以尽量减少残留效应。使用移动间隔平均技术测量并总结24小时收缩压、舒张压和心率。使用协方差分析（SAS）分别比较总队列以及单纯收缩期高血压组和对照组中各治疗组间24小时收缩压、舒张压、心率、尿钠、钾、蛋白和肌酐、肌酐清除率及血清电解质的平均变化。
在总队列中，与低氯化钠组相比，慢性高氯化钠组使平均收缩压升高（5.76 mmHg；P = 0.0002），舒张压升高（3.36 mmHg；P = 0.002）。吲哚美辛显著升高平均收缩压（2.66 mmHg，P = 0.015），但未显著升高舒张压（0.31 mmHg，P = 0.419）。高盐和I具有相加作用（收缩压总和、舒张压总和），但无相互作用（分别为P = 0.795和P = 0.七十三九）。此外，正如预期的那样，慢性高氯化钠组使血清钠（P = 0.0001）和24小时尿钠升高（P = 0.0001）。吲哚美辛显著降低平均心率（P = 0.018）。氯化钠和I对收缩压、舒张压和心率的影响不受年龄、酒精摄入量、血清钾、体重指数或治疗顺序的影响。在单纯收缩期高血压组中，氯化钠剂量显著升高收缩压（9.87 mmHg；P = 0.0001）和舒张压（5.26 mmHg，P = 0.006），但在血压正常组中未显著改变血压。吲哚美辛在血压正常个体中显著升高收缩压（P = 0.03），但在单纯收缩期高血压组中对血压无影响。
在老年人群总队列中，慢性高盐饮食比吲哚美辛更能升高血压。未显示出相互作用，二者作用具有相加性。在单纯收缩期高血压组中，慢性高盐饮食显著升高收缩压和舒张压，而吲哚美辛未能改变血压。在血压正常组中，吲哚美辛升高收缩压，而盐无此作用。与老年血压正常的对照个体相反，单纯收缩期高血压患者对氯化钠的升压作用敏感，但对前列腺素抑制的升压作用有抗性。
