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Angiotensin II Receptor Blocker Candesartan Cilexetil, but Not Hydralazine Hydrochloride, Protects Against Mouse Cardiac Enlargement Resulting From Undernutrition In Utero

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Hiroaki Itoh, MD, D Med Sci

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan, hitouendo{at}umin.ac.jp

Shigeo Yura, MD, PhD

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Haruta Mogami, MD

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Tsuyoshi Fujii, MD

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Naohiro Kanayama, MD, PhD

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Ikuo Konishi, MD, PhD

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

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.

Key Words: DOHaD • pregnancy • nutrition • cardiac remodeling.

This version was published on October 1, 2009

Reproductive Sciences, Vol. 16, No. 10, 1005-1012 (2009)
DOI: 10.1177/1933719109345610


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