Article

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
Hypertension (Impact Factor: 6.48). 02/2010; 55(2):270-6. DOI: 10.1161/HYPERTENSIONAHA.109.142042
Source: PubMed

ABSTRACT

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.

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    • "Interestingly , transfected mice missing TAC1 gene were protected against cardiac hypertrophy and dilatation of the left ventricle (Melendez et al., 2011). SP may also be operative in modulating the inflammation in hypertensive heart disease (Levick et al., 2010). SP probably plays an important role in the cardiac fibrosis, where it induces adverse myocardial remodelling via a mechanism involving cardiac mast cells (Melendez et al., 2011). "
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    • "Both parasite and viral infection of the heart results in dramatic increases in myocardial substance P levels that appears to regulate cardiomyocyte death, hypertrophy, necrosis and inflammation [9]. SP may also be operative in modulating the inflammation in hypertensive heart disease [33]. Chagas disease cardiomyopathy belongs into this group of cardiomyopathies. "
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    • "Both parasite and viral infection of the heart results in dramatic increases in myocardial substance P levels that appears to regulate cardiomyocyte death, hypertrophy, necrosis and inflammation [9]. SP may also be operative in modulating the inflammation in hypertensive heart disease [33]. Chagas disease cardiomyopathy belongs into this group of cardiomyopathies. "
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    ABSTRACT: The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides - Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy-diabetic, ischemic, inflammatory, stress-induced or restricitive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.
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