Abstract
IntroductionThe G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure.MethodsIntact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for 10 weeks beginning at 5 weeks of age.ResultsProlonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e′)] independent of prevailing salt, and improved the e′/a′ ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler.ConclusionActivation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.
Highlights
The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart
Hypertension in postmenopausal women results in left ventricular hypertrophy (LVH), a major causative factor for reductions in both myocardial relaxation and diastolic compliance which are key components of diastolic dysfunction [1,2,3]
To determine whether cardiac GPER gene expression was altered by high salt, we utilized real-time PCR to compare GPER mRNA in hearts from female mRen2.Lewis rats fed a normal salt (NS) or high salt (HS) diet
Summary
The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure. Saltsensitive hypertensive patients have a higher incidence of LVH than salt-resistant hypertensive individuals [5], further increasing their predisposition for the development of diastolic heart disease. While evidence suggests that estrogen may protect the premenopausal heart from the deleterious effects of hypertension and salt-induced LV remodeling [7,8], the mechanisms and receptors involved remain unclear. Estrogen attenuates the development of cardiac hypertrophy and fibrosis through activation of steroid receptors ERa and ERb located on myocytes, fibroblasts, and the extracellular matrix [9]. GPER activation improves contractile function and reduces infarct size in isolated rat and mouse hearts subjected to ischemia/reperfusion injury [14]; the precise role for GPER in cardiac remodeling is not known
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
