Nishi Isao, Kawano Satoru, Misaki Masako, Hoshi Tomoya, Masumi Tomoko, Iida Keiji, Watanabe Shigeyuki, Yamaguchi Iwao
Graduate School of Comprehensive Human Science, Medicine of Cardiovascular Pathophysiology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Heart Vessels. 2006 Jul;21(4):251-5. doi: 10.1007/s00380-005-0898-5.
We investigated the effect of adding spironolactone to treatment with an angiotensin-converting enzyme (ACE) inhibitor, imidapril, in Dahl salt-sensitive (DS) hypertensive heart failure rats with preserved systolic function. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Rats were divided into four groups and treated for 9 weeks with vehicle alone (water; n = 23), the ACE inhibitor imidapril (1 mg kg(-1) day(-1); n = 16), spironolactone (2 mg kg(-1) day(-1); n = 15), or a combination of imidapril and spironolactone at the doses above (n = 16). The left ventricular weight to body weight (BW) ratio was significantly lower in the imidapril group (3.28 +/- 0.30 mg g(-1)) and the combination group (3.34 +/- 0.38 mg g(-1)) than in the vehicle group (3.71 +/- 0.46 mg g(-1)). Adding spironolactone to imidapril inhibited an increase in the ratio of lung weight to BW (4.38 +/- 0.50 mg g(-1)) related to high salt intake, while monotherapy (imidapril group, 4.61 +/- 0.90 mg g(-1); spironolactone group, 5.40 +/- 2.50) did not significantly change the ratio from that seen with vehicle treatment (6.32 +/- 3.62 mg g(-1)). All active treatments (imidapril, 0.66% +/- 0.67%; spironolactone, 0.51% +/- 0.55%; both together, 0.31% +/- 0.26%) inhibited a salt-intake related increase in the percentage area representing fibrous tissue compared with vehicle treatment alone (1.81% +/- 1.51%). These findings suggest that adding spironolactone to an ACE inhibitor is more effective in improving pulmonary congestion and edema in hypertensive heart failure with preserved systolic function than an ACE inhibitor alone.
我们研究了在收缩功能保留的Dahl盐敏感（DS）高血压心力衰竭大鼠中，将螺内酯添加到血管紧张素转换酶（ACE）抑制剂咪达普利治疗中的效果。雄性DS大鼠从7周龄开始喂食含8%氯化钠的实验室饲料。大鼠被分为四组，分别用单独的赋形剂（水；n = 23）、ACE抑制剂咪达普利（1 mg kg⁻¹ day⁻¹；n = 16）、螺内酯（2 mg kg⁻¹ day⁻¹；n = 15）或上述剂量的咪达普利与螺内酯联合用药（n = 16）治疗9周。咪达普利组（3.28 ± 0.30 mg g⁻¹）和联合用药组（3.34 ± 0.38 mg g⁻¹）的左心室重量与体重（BW）之比显著低于赋形剂组（3.71 ± 0.46 mg g⁻¹）。在咪达普利中添加螺内酯可抑制与高盐摄入相关的肺重量与BW之比（4.38 ± 0.50 mg g⁻¹）的增加，而单一疗法（咪达普利组，4.61 ± 0.90 mg g⁻¹；螺内酯组，5.40 ± 2.50）与赋形剂治疗相比（6.32 ± 3.62 mg g⁻¹）并未显著改变该比值。与单独使用赋形剂治疗（1.81% ± 1.51%）相比，所有活性治疗（咪达普利，0.66% ± 0.67%；螺内酯，0.51% ± 0.55%；两者联合，0.31% ± 0.26%）均抑制了代表纤维组织的面积百分比与盐摄入相关的增加。这些发现表明，在收缩功能保留的高血压心力衰竭中，在ACE抑制剂基础上加用螺内酯在改善肺充血和水肿方面比单独使用ACE抑制剂更有效。
