Teräväinen T L, Mervaala E M, Pörsti I, Laakso J, Vapaatalo H, Karppanen H
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Methods Find Exp Clin Pharmacol. 1997 Jun;19(5):311-21.
The aim of the present study was to investigate the influence of age and an increased intake of dietary sodium on the cardiovascular and renal effects of the angiotensin converting enzyme inhibitor, ramipril. Male spontaneously hypertensive rats (SHR) aged 10 and 60 weeks received either control or a high level of sodium (0.3% vs. 2.6% Na) and ramipril (2 mg/kg/day) mixed in the chow for 6 weeks. Blood pressure was measured weekly by tail-cuff method. Arterial functions were determined by measuring vascular contractile and relaxation responses of mesenteric arterial rings in vitro at the end of the study. An age-related increase in systolic blood pressure, left ventricular (LVH) and renal hypertrophy (RH) as well as proteinuria were found in SHR. The vascular relaxation to nitroprusside was impaired in aged SHR. The high sodium intake accelerated the development of hypertension only in young SHR but increased LVH and RH in both age groups. Ramipril effectively lowered blood pressure in both age groups, but decreased the LVH significantly only in young rats. Ramipril markedly improved the vascular relaxation to acetylcholine and nitroprusside only in young rats. The vascular contractile responses to noradrenaline and potassium chloride were not affected by age, sodium intake or ramipril treatment. The high sodium intake markedly attenuated the cardiovascular effects of ramipril. The high-sodium diet enhanced the urinary excretion of cyclic GMP in both age groups, while it increased urinary excretion of protein in young SHR only. In conclusion, the cardiovascular effects of ramipril were impaired with advanced age even in the presence of a control intake of sodium. A high sodium intake attenuated or even abolished the cardiovascular effects of ramipril in both young and aged SHR.
本研究的目的是调查年龄和饮食中钠摄入量增加对血管紧张素转换酶抑制剂雷米普利的心血管和肾脏效应的影响。10周龄和60周龄的雄性自发性高血压大鼠（SHR）分别接受对照饮食或高钠饮食（0.3%钠 vs. 2.6%钠），并在食物中混入雷米普利（2 mg/kg/天），持续6周。每周通过尾袖法测量血压。在研究结束时，通过体外测量肠系膜动脉环的血管收缩和舒张反应来确定动脉功能。在SHR中发现收缩压、左心室肥厚（LVH）和肾肥厚（RH）以及蛋白尿随年龄增长而增加。老年SHR对硝普钠的血管舒张功能受损。高钠摄入仅在年轻SHR中加速了高血压的发展，但在两个年龄组中均增加了LVH和RH。雷米普利在两个年龄组中均有效降低了血压，但仅在年轻大鼠中显著降低了LVH。雷米普利仅在年轻大鼠中显著改善了对乙酰胆碱和硝普钠的血管舒张功能。对去甲肾上腺素和氯化钾的血管收缩反应不受年龄、钠摄入或雷米普利治疗的影响。高钠摄入显著减弱了雷米普利的心血管效应。高钠饮食在两个年龄组中均增加了环磷酸鸟苷的尿排泄，而仅在年轻SHR中增加了蛋白质的尿排泄。总之，即使在钠摄入量正常的情况下，雷米普利的心血管效应也会随着年龄的增长而受损。高钠摄入在年轻和老年SHR中均减弱甚至消除了雷米普利的心血管效应。
