Angiotensin II Receptor Blocker Candesartan Cilexetil, but Not Hydralazine Hydrochloride, Protects Against Mouse Cardiac Enlargement Resulting From Undernutrition In Utero
Angiotensin II Receptor Blocker Candesartan Cilexetil, but Not Hydralazine Hydrochloride, Protects Against Mouse Cardiac Enlargement Resulting From Undernutrition In Utero
复制标题
DOI：
10.1177/1933719109345610
复制
发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
--
作者：
Kawamura, Makoto;Itoh, Hiroaki;Konishi, Ikuo
流行病学研究表明，子宫内营养不良是成年后心血管疾病（CVD）的危险因素。最近，我们报道了一种母体热量减少 30% 的小鼠动物模型，其中成年后代（营养不良 [UN] 后代）表现出心脏重塑相关参数显着增加，如心脏扩大 (CE) 和冠状动脉周围纤维化 (CPVF)，作为 CVD 的危险因素。为了研究血管紧张素系统可能的参与情况，在出生后 9 至 17 周，通过皮下植入的微渗泵给 UN 后代施用血管紧张素 II 受体拮抗剂坎地沙坦西酯或非特异性血管扩张剂盐酸肼苯达嗪。给予坎地沙坦西酯，但不使用盐酸肼屈嗪，可显着预防 CE。同时，不仅给予坎地沙坦西酯，而且给予盐酸肼苯达嗪也可防止 CPVF 的增加。血管紧张素系统似乎对心脏扩大的发育起源做出了关键贡献。
Epidemiologic studies have shown that malnutrition in utero is a risk factor for cardiovascular disease (CVD) in adulthood. Recently, we reported a mouse animal model of 30% maternal caloric reduction, in which adult offspring (undernourished [UN] offspring) showed a significant increase in cardiac remodeling-associated parameters, such as cardiac enlargement (CE) and coronary perivascular fibrosis (CPVF), as risk factors for CVD. To investigate the possible involvement of the angiotensin system, an angiotensin II receptor antagonist, candesartan cilexetil, or a nonspecific vasodilator, hydralazine hydrochloride, was administrated via a subcutaneously implanted miniosmotic pump to the UN offspring from 9 to 17 weeks after birth. Administration of candesartan cilexetil, but not hydralazine hydrochloride, significantly protected against CE. While administration of not only candesartan cilexetil but also hydralazine hydrochloride prevented an augmentation of CPVF. The angiotensin system seems to make a critical contribution to the developmental origins of cardiac enlargement.