Sympathetic nervous system modulation of inflammation and remodeling in the hypertensive heart. Hypertension 2010 Feb;55(2):270-6
Date
01/06/2010Pubmed ID
20048196Pubmed Central ID
PMC2823485DOI
10.1161/HYPERTENSIONAHA.109.142042Scopus ID
2-s2.0-74949095694 (requires institutional sign-in at Scopus site) 136 CitationsAbstract
Chronic activation of the sympathetic nervous system is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence that also implicate inflammatory cells, including mast cells (MCs), in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac MCs with the sympathetic nervous system. Eight-week-old male spontaneously hypertensive rats were sympathectomized to establish the effect of the sympathetic nervous system on cardiac MC density, myocardial remodeling, and cytokine production in the hypertensive heart. Age-matched Wistar Kyoto rats served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized, whereas cardiac MC density was markedly increased in sympathectomized spontaneously hypertensive rats. Sympathectomy normalized myocardial levels of interferon-gamma, interleukin 6, and interleukin 10, but had no effect on interleukin 4. The effects of norepinephrine and substance P on isolated cardiac MC activation were investigated as potential mechanisms of interaction between the two. Only substance P elicited MC degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including MCs, lymphocytes, and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the sympathetic nervous system and afferent nerves may interact with inflammatory cells in the hypertensive heart.
Author List
Levick SP, Murray DB, Janicki JS, Brower GLMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAngiotensin II
Animals
Cardiomegaly
Cells, Cultured
Cytokines
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Hypertension
Inflammation Mediators
Male
Myocytes, Cardiac
Probability
Random Allocation
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Substance P
Sympathectomy
Sympathetic Nervous System
Ventricular Remodeling
