Asai Takae, Kushiro Toshio, Fujita Hirotaka, Kanmatsuse Katsuo
Division of Cardiovascular Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hypertens Res. 2005 Jan;28(1):79-87. doi: 10.1291/hypres.28.79.
To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1 receptor blockers (ARBs) have different abilities to attenuate progressive cardiac hypertrophy despite their comparable lowering of blood pressure, we compared the effect of these agents alone or in combination on hypertensive cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were divided into 7 groups. Single administration of doxazosin, atenolol, or losartan, or half-dose combinations of these drugs were given orally for 6 weeks. The control group did not receive any drugs. The heart weight-to-body weight ratio (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide (BNP) and left ventricular BNP mRNA expression were measured after 6-week administration. Blood pressure did not differ among the drug-treated groups, all of which showed lower blood pressure than the control group. The HW/BW and LVMI of the drug-treated groups, except the doxazosin group, were lower than in the control group. Moreover, the LVMI values of the groups receiving losartan were significantly lower than those in the groups without losartan (p < 0.05). Plasma BNP of the drug-treated groups was lower than that in the control group (p < 0.05). The left ventricular BNP mRNA expression of the drug-treated groups, except the doxazosin group, was lower than that in the control group. The atenolol group showed a higher level of BNP mRNA than the groups receiving losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB had the strongest attenuating effect on the development of hypertensive cardiac hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more effective in combination than as monotherapies in SHR.
为了证实α1、β肾上腺素能受体拮抗剂和血管紧张素II 1型受体阻滞剂（ARB）尽管在降低血压方面效果相当，但在减轻进行性心脏肥大方面具有不同的能力，我们比较了这些药物单独使用或联合使用对高血压性心脏肥大的影响。将8周龄的自发性高血压大鼠（SHR）分为7组。口服给予多沙唑嗪、阿替洛尔或氯沙坦单药治疗，或这些药物的半量联合治疗，持续6周。对照组未接受任何药物治疗。给药6周后测量心脏重量与体重比（HW/BW）、左心室质量指数（LVMI）、血浆脑钠肽（BNP）和左心室BNP mRNA表达。各药物治疗组的血压无差异，且均低于对照组。除多沙唑嗪组外，各药物治疗组的HW/BW和LVMI均低于对照组。此外，接受氯沙坦治疗组的LVMI值显著低于未接受氯沙坦治疗组（p<0.05）。各药物治疗组的血浆BNP均低于对照组（p<0.05）。除多沙唑嗪组外，各药物治疗组的左心室BNP mRNA表达均低于对照组。阿替洛尔组的BNP mRNA水平高于接受氯沙坦单药治疗或联合治疗的组（p<0.05）。总之，ARB对高血压性心脏肥大的发展具有最强的减轻作用，在SHR中，α1和β肾上腺素能受体阻滞剂联合使用比单药治疗更有效。
