Chan J C, Nicholls M G, Cheung C K, Law L K, Swaminathan R, Cockram C S
Department of Clinical Pharmacology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin.
Diabetes Care. 1995 Jul;18(7):1001-6. doi: 10.2337/diacare.18.7.1001.
To examine the factors that determine the blood pressure response to enalapril and nifedipine monotherapy in the treatment of hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM).
After a 6-week placebo baseline period, 102 hypertensive NIDDM patients were randomly assigned, double-blindly, to treatment with nifedipine retard (slow release) (n = 52) or enalapril (n = 50). The daily dosage of enalapril was increased, if required, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pressure, 24-h urinary albumin excretion (UAE), biochemical data, and serum angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and serum insulin concentrations.
At week 12, the mean daily dose of enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving the maximum daily dose of 40 mg. In the nifedipine group, the mean daily drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE activity in the enalapril group, the mean arterial pressure (MAP) was reduced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectively, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone concentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MAP and baseline plasma renin concentration. On multivariate analysis, the baseline renal function, glycemic control, and plasma aldosterone and serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such statistical associations were observed in the nifedipine group.
In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may optimize the antihypertensive efficacy of concomitant ACE inhibitor therapy.
研究在治疗非胰岛素依赖型糖尿病（NIDDM）相关高血压时，决定血压对依那普利和硝苯地平单药治疗反应的因素。
在为期6周的安慰剂基线期后，102例高血压NIDDM患者被随机双盲分配至硝苯地平缓释片治疗组（n = 52）或依那普利治疗组（n = 50）。在12周的滴定期内，每隔4周，依那普利的每日剂量根据需要从10 mg增至20 mg再增至40 mg，硝苯地平的每日剂量从40 mg增至60 mg再增至80 mg。在第-6、-4、0、4、8和12周测量血压、24小时尿白蛋白排泄量（UAE）、生化数据以及血清血管紧张素转换酶（ACE）活性。在第0周，还采集静脉血以测定基线血浆心钠素、肾素、醛固酮和血清胰岛素浓度。
在第12周，依那普利的平均每日剂量为35±11.4 mg，27例（57%）患者接受最大每日剂量40 mg。在硝苯地平组，平均每日药物剂量为50±12.9 mg，4例（8%）患者接受最大每日剂量80 mg。尽管依那普利组血清ACE活性呈剂量依赖性下降，但在整个12周滴定期内，平均动脉压（MAP）仅降低了8 mmHg，而硝苯地平组在第0、4和12周分别下降了15、18和19 mmHg（两组间P = 0.01）。在依那普利组，第0周和第12周之间MAP的变化与基线血浆葡萄糖（r = 0.45，P = 0.001）、醛固酮浓度（r = -0.32，P = 0.02）和UAE（r = 0.3，P = 0.04）显著相关。MAP变化与基线血浆肾素浓度之间无统计学显著相关性。多因素分析显示，基线肾功能、血糖控制、血浆醛固酮和血清胰岛素浓度均与依那普利治疗患者的血压变化独立相关。在硝苯地平组未观察到此类统计学关联。
在高血压NIDDM患者中，肾素-血管紧张素-醛固酮系统的活性、血清胰岛素水平、血糖控制、肾功能和蛋白尿可能是血压对ACE抑制反应的重要决定因素。良好的血糖控制可能会优化同时使用ACE抑制剂治疗的降压疗效。
