Premium
Prevention of Volume Overload‐Induced Adverse Myocardial Remodeling in Neurokinin‐1 Receptor Knockout Mice
Author(s) -
Levick Scott P,
Melendez Giselle C,
Li Jianping,
Supowit Scott C,
Brower Gregory L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.812.2
Subject(s) - receptor , knockout mouse , volume overload , substance p , medicine , endocrinology , fistula , ejection fraction , ventricular remodeling , inflammation , pressure overload , neuropeptide , heart failure , surgery , cardiac hypertrophy
The neurokinin‐1 (NK‐1) receptor is the high affinity receptor for the neuropeptide, substance P, which is predominantly released from sympathetic afferent nerve fibers and is important in many diseases involving inflammation. We sought to determine the importance of the NK‐1 receptor to adverse myocardial remodeling in response to volume overload induced in 3 month old NK‐1 knockout (KO) (n=6) mice by creation of an aortacaval fistula. Age‐matched C57B/6 mice (fistula, n=5; shams, n=3) served as wild type controls. Mice were followed by echocardiography for 14 days post‐fistula to assess in vivo left ventricular (LV) structure and function. Wild type mice showed LV dilatation at 10 and 14 days post‐fistula, which did not occur in NK‐1 KO mice. LV posterior wall thickening was evident at 14 days post‐fistula in NK‐1 KO mice, but not in wild type, suggesting an adaptive response to increased wall stress in the NK‐1 KO. Ejection fraction decreased 3 days post‐fistula in both groups, returning to normal at 14 days post fistula in NK‐1 KO mice, but not in wild type. Thus, deletion of the NK‐1 receptor in mice exposed to volume overload prevented adverse myocardial remodeling in the form of LV dilatation, and restored systolic function. This study demonstrates for the first time the potential critical role for substance P, acting via the NK‐1 receptor, in adverse myocardial remodeling.