title: Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Middle-aged, Ovariectomized Fischer 344 × Brown Norway Rats.
abstract: The incidence of left ventricular diastolic dysfunction (LVDD) increases in women after menopause, yet the mechanisms are unclear. Because mast cells participate in the pathological processes of various cardiac diseases, we hypothesized that mast cell inhibition would protect against estrogen loss-induced LVDD. The mast cell stabilizer, cromolyn sodium (30 mg·kg·d), or vehicle was administered subcutaneously by osmotic minipump to ovariectomized (OVX) female Fischer 344 × Brown Norway (F344BN) rats starting at 4 weeks after surgery. Eight weeks after OVX, systolic blood pressure increased by 20% in OVX versus sham rats, and this effect was attenuated after 4 weeks of cromolyn treatment. Also, cromolyn mitigated the adverse reductions in myocardial relaxation (e') and increases in left ventricle (LV) filling pressures (E/e'), LV mass, wall thicknesses, and interstitial fibrosis from OVX. Although cardiac mast cell number was increased after OVX, cardiac chymase activity was not overtly altered by estrogen status and tended to decrease by cromolyn. Contrariwise, Ang II content was greater in hearts of OVX versus sham rats, and cromolyn attenuated this effect. Taken together, mast cell inhibition with cromolyn attenuates LV remodeling and LVDD in OVX-Fischer 344 × Brown Norway rats possibly through actions on the heart level and/or through vasodilatory effects at the vascular level.
authors.affiliation: *Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC;†Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC;‡Institute of Biomedical Sciences, Drug Development Program, Federal University of Rio de Janeiro, Brazil;§Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC;¶Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC;‖Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC; and**Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jaqueline
authors.initials: J
authors.lastname: da Silva
authors.forename: Allan
authors.initials: A
authors.lastname: Alencar
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
authors.forename: Marina R
authors.initials: MR
authors.lastname: Lin
authors.forename: Xuming
authors.initials: X
authors.lastname: Sun
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D053818:Chymases / Q000378:metabolism; D004205:Cromolyn Sodium / Q000008:administration & dosage*; D003433:Crosses, Genetic; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D004967:Estrogens / Q000097:blood; D005260:Female; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D055104:Infusions, Subcutaneous; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D004967:Estrogens; D000804:Angiotensin II; D053818:Chymases; D004205:Cromolyn Sodium