Angiotensin type 1 receptor blockade prevents cardiac remodeling in mice with pregnancy-associated hypertension.

Abstract

Pregnancy-induced hypertension (PIH) is a life-threatening disorder for both mother and fetus; cardiac dysfunction is the major complication and can result in further deterioration. Recently, it has been recognized that aberrant activation of angiotensin type 1 receptor (AT1) signaling contributes to the pathogenesis of PIH, but the details of the relationship between cardiac injury and enhanced AT1 signaling in PIH are still unclear. We previously generated a transgenic mouse model of pregnancy-associated hypertension (PAH) via overproduction of angiotensin II, an endogenous ligand of AT1, in the maternal circulation during late pregnancy. In the present study, we administered olmesartan, an AT1 blocker, to suppress redundant AT1 signaling in PAH mice and evaluated the efficacy of this treatment in cardiac remodeling. Olmesartan treatment significantly lowered the blood pressure of PAH mice, and hypertrophy as well as increased plasma levels of cardiac injury markers were also markedly reduced. Histological analyses revealed that morphological abnormalities and fibrosis in the hearts of PAH mice recovered to the levels of normal pregnant wild-type mice after the administration of olmesartan. Moreover, in fibrotic regions of PAH hearts, olmesartan treatment significantly decreased the extent of cardiac injury and apoptosis. These results indicate that the activation of AT1 signaling pathways during maternal hypertension plays a critical role in cardiac remodeling in PAH mice, and suggest that treatment with an AT1 blocker could effectively ameliorate cardiac dysfunction during pregnancy with hypertension in vivo.

• Authors: Akira Sakairi, Junji Ishida, Kaori Honjo, Saki Inaba, Shoko Nakamura, Fumihiro Sugiyama, Ken-Ichi Yagami, Akiyoshi Fukamizu
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 31 Issue 12 Pg. 2165-75 (Dec 2008) ISSN: 0916-9636 [Print] England
• PMID: 19139606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Imidazoles
• Receptor, Angiotensin, Type 1
• Tetrazoles
• olmesartan

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Blood Pressure (drug effects, physiology)
• Cardiomegaly (physiopathology, prevention & control)
• Disease Models, Animal
• Female
• Fibrosis
• Hypertension, Pregnancy-Induced (physiopathology)
• Imidazoles (pharmacology)
• Male
• Mice
• Mice, Transgenic
• Myocardium (pathology)
• Pregnancy
• Receptor, Angiotensin, Type 1 (drug effects, physiology)
• Signal Transduction (drug effects, physiology)
• Tetrazoles (pharmacology)
• Ventricular Remodeling (drug effects, physiology)