Abstract P285: Diastolic Dysfunction After Estrogen Loss is Linked to Cardiac Chymase in WKY but Not SHR Rats

Abstract

Left ventricular diastolic dysfunction (LVDD) develops in response to hypertension and estrogen (E2) loss and is consequent to heart failure in women. To understand the mechanisms underlying the development of LVDD as a result of the interaction between E2 loss and the cardiac RAS, we compared the relationships of LV tissue RAS components and E/e′ between adult SHR (n=13) and WKY (n=9) female rats after ovariectomy (OVX) or sham surgery (intact). In intact rats, E/e′ was higher in SHR vs. WKY rats (P<0.05 strain effect) and after OVX, the diastolic phenotype of WKY’s mimicked that of intact SHR counterparts (Figure). While relationships between RAS enzymatic activities and E/e′ were not significant in SHRs with respect to estrogen status (data not shown), OVX-induced increases in E/e′ were significantly linked to increases in chymase gene expression and enzymatic activity in the WKY strain (Figure). These data indicate that 1) the altered diastolic function in SHR is relatively insensitive to loss of estrogen while the opposite is true in WKY rats, and 2) OVX-induced LVDD in WKY is directly related to increases in cardiac chymase activity. Further elucidation of the interplay between an activated cardiac chymase-mediated RAS metabolism and LVDD following estrogen loss in normotensive subjects is warranted.