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Substance P mediated myocardial remodeling in the hypertensive heart
Author(s) -
Levick Scott P,
Melendez Giselle C,
Spencer William J
Publication year - 2011
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.25.1_supplement.1031.7
Subject(s) - medicine , substance p , ventricle , endocrinology , angiotensin ii , fibrosis , inflammation , ventricular remodeling , muscle hypertrophy , blood pressure , receptor , heart failure , neuropeptide
Substance P, which is found in sensory nerves, has recently been shown to mediate adverse myocardial remodeling following initiation of myocarditis in mice. We sought to determine whether substance P and its receptor, the neurokinin‐1 (NK‐1) receptor also play a role in adverse remodeling stemming from systemic hypertension. Accordingly, 12 week old spontaneously hypertensive rats (SHR) were treated for 3 weeks with the NK‐1 receptor antagonist L 732 138 (5mg/kg/d). Antagonism of the NK‐1 receptor normalized cardiac fibrosis in the left ventricle (LV) while hypertrophy remained unchanged. The effect on remodeling was independent of blood pressure since the SHR remained hypertensive. Inflammation is an important component of the fibrotic response in the hypertensive left ventricle. We isolated inflammatory cells, including T cells, mast cells and macrophages, from the LV of rats and incubated them with substance P. Substance P stimulated production of angiotensin II and TNF‐α by this mixed population of inflammatory cells. Thus, substance P activation of inflammatory cells results in the local production of angiotensin II and TNF‐α which are known to lead to adverse remodeling in the hypertensive heart. This work was supported by award number K99HL093215 from the National Heart, Lung, And Blood Institute.