da Silva Jacqueline S, Gabriel-Costa Daniele, Wang Hao, Ahmad Sarfaraz, Sun Xuming, Varagic Jasmina, Sudo Roberto T, Ferrario Carlos M, Dell Italia Louis J, Sudo Gisele-Zapata, Groban Leanne
1 Research Program Development of Drugs, Institute of Biomedical Sciences Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
2 The Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA.
J Renin Angiotensin Aldosterone Syst. 2017 Jul-Sep;18(3):1470320317722270. doi: 10.1177/1470320317722270.
Diastolic dysfunction develops in response to hypertension and estrogen (E2) loss and is a forerunner to heart failure (HF) in women. The cardiac renin-angiotensin system (RAS) contributes to diastolic dysfunction, but its role with respect to E2 and blood pressure remain unclear.
We compared the effects of ovariectomy (OVX) or sham surgery on the cardiac RAS, left ventricular (LV) structure/function, and systemic/intracardiac pressures of spontaneously hypertensive rats (SHRs: n = 6 intact and 6 OVX) and age-matched Wistar-Kyoto (WKY: n = 5 intact and 4 OVX) controls.
WKY rats were more sensitive to OVX than SHRs with respect to worsening of diastolic function, as reflected by increases in Doppler-derived filling pressures (E/e') and reductions in myocardial relaxation (e'). This pathobiologic response in WKY rats was directly linked to increases in cardiac gene expression and enzymatic activity of chymase and modest reductions in ACE2 activity. No overt changes in cardiac RAS genes or activities were observed in SHRs, but diastolic function was inversely related to ACE2 activity.
Endogenous estrogens exert a more significant regulatory role upon biochemical components of the cardiac RAS of WKY versus SHRs, modulating the lusitropic and structural components of its normotensive phenotype.
舒张功能障碍是对高血压和雌激素（E2）丧失的反应，是女性心力衰竭（HF）的先兆。心脏肾素-血管紧张素系统（RAS）导致舒张功能障碍，但其在E2和血压方面的作用仍不清楚。
我们比较了卵巢切除术（OVX）或假手术对自发性高血压大鼠（SHRs：n = 6只完整和6只OVX）以及年龄匹配的Wistar-Kyoto（WKY：n = 5只完整和4只OVX）对照的心脏RAS、左心室（LV）结构/功能以及全身/心内压力的影响。
就舒张功能恶化而言，WKY大鼠比SHRs对OVX更敏感，这通过多普勒衍生的充盈压（E/e'）增加和心肌松弛（e'）降低反映出来。WKY大鼠的这种病理生物学反应与糜酶的心脏基因表达和酶活性增加以及ACE2活性适度降低直接相关。在SHRs中未观察到心脏RAS基因或活性的明显变化，但舒张功能与ACE2活性呈负相关。
内源性雌激素对WKY大鼠心脏RAS生化成分的调节作用比对SHRs更显著，调节其正常血压表型的舒张期和结构成分。
