The incidence of left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD) increases in postmenopausal women, but the mechanisms are not yet clear. This study determined the cardioprotective effects of chronic mast cell inhibition by the mast cell stabilizer, cromolyn sodium, in middle-aged (18-month-old), female Fischer344хBrown Norway (F344BN) rats after estrogen (E2) loss by ovariectomy (OVX). Eight weeks after OVX, systolic blood pressure increased in OVX vs. sham-operated rats (141±6 vs. 108±4 mmHg, P<0.05), and cromolyn treatment (30 mg/kg/day x 4 weeks, s.c. via osmotic minipump, n=7/group), initiated one month after OVX, attenuated this effect (115±4 mmHg). Myocardial relaxation (e') was reduced, LV filling pressures (E/e') were increased, and LV mass, wall thicknesses, and percent interstitial fibrosis were increased in OVX vs. sham rats. All of these cardiac adverse effects of E2 loss were mitigated by cromolyn treatment (Figure). Cardiac mast cell number was increased after OVX, irrespective of cromolyn. While no differences in plasma angiotensin (Ang) II levels were observed between OVX and sham rats (33.7±4.6 vs. 32.0±4.5 pg/mL), plasma levels of Ang II were reduced in cromolyn-treated OVX rats (21.3±3.0 pg/mL) (P<0.05 vs. sham and OVX-vehicle). Ang II content was significantly increased in hearts of OVX vs. sham rats, and cromolyn attenuated this effect. Moreover, cromolyn prevented the increase in cardiac Ang II type 1 receptor (AT1aR) mRNA expression in OVX rats. Our findings demonstrate that mast cell inhibition with cromolyn attenuates adverse LV remodeling and LVDD in OVX-F344BN rats possibly through a chymase/Ang II-mediated mechanism.
Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats