Carraway J W, Park S, McCune S A, Holycross B J, Radin M J
Department of Veterinary Biosciences, The Ohio State University, Columbus, USA.
J Cardiovasc Pharmacol. 1999 Mar;33(3):451-60. doi: 10.1097/00005344-199903000-00016.
Angiotensin-converting enzyme (ACE) inhibitors have proven an effective means to control hypertension and manage cardiac hypertrophy. It is presently unknown if newer specific angiotensin II subtype 1 receptor (AT1R) antagonists are as effective or more effective in treating these conditions compared with ACE inhibitors. There is evidence that these classes of drugs may affect cardiac hypertrophy by different mechanisms. This study compared the effect of irbesartan, an AT1R antagonist, with that of captopril, an ACE inhibitor, on expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc-fa(cp) rats. SHHF/Mcc-fa(cp) rats (n = 10/group) were given captopril (100 mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and captopril significantly reduced systolic pressure and produced similar rightward shifts in the angiotensin I dose-response curve. Renal renin gene expression was increased 8.6-fold by irbesartan and 17.7-fold by captopril. The only effect on echocardiographic findings was a similar decrease in aortic peak velocity, an index of systolic function, by both treatments. Early markers of cardiac hypertrophy were significantly attenuated by both drugs. Both drugs produced marked and equivalent reductions in left ventricular atrial natriuretic peptide (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP gene expression was accompanied by a decrease in plasma ANP concentration in the treatment groups. The shift from V1 to V3 myosin isozymes was similarly decreased in both treatment groups, compared with controls. These data suggest that captopril and irbesartan are similarly effective in controlling expression of genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc-fa(cp) rat.
血管紧张素转换酶（ACE）抑制剂已被证明是控制高血压和治疗心脏肥大的有效手段。目前尚不清楚与ACE抑制剂相比，新型特异性血管紧张素II 1型受体（AT1R）拮抗剂在治疗这些疾病方面是否同样有效或更有效。有证据表明，这类药物可能通过不同机制影响心脏肥大。本研究比较了AT1R拮抗剂厄贝沙坦与ACE抑制剂卡托普利对易患心力衰竭的瘦雄性SHHF/Mcc-fa(cp)大鼠心脏肥大早期基因标志物表达的影响。将SHHF/Mcc-fa(cp)大鼠（每组n = 10）给予卡托普利（100 mg/kg/天）、厄贝沙坦（50 mg/kg/天）或安慰剂，持续16周。厄贝沙坦和卡托普利显著降低收缩压，并使血管紧张素I剂量反应曲线产生类似的右移。厄贝沙坦使肾素基因表达增加8.6倍，卡托普利使其增加17.7倍。两种治疗对超声心动图检查结果的唯一影响是，二者均使主动脉峰值速度（收缩功能指标）出现类似程度的降低。两种药物均显著减轻了心脏肥大的早期标志物。与对照组相比，两种药物均使左心室心房利钠肽（ANP）信使核糖核酸（mRNA）水平显著降低且程度相当。治疗组中ANP基因表达的这种降低伴随着血浆ANP浓度的下降。与对照组相比，两个治疗组中从V1型肌球蛋白向V3型肌球蛋白的转变同样减少。这些数据表明，卡托普利和厄贝沙坦在控制易患心力衰竭的SHHF/Mcc-fa(cp)大鼠心室肥大相关基因的表达方面同样有效。
