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: 7.63). 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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    ABSTRACT: Heart failure with preserved left ventricular ejection fraction (HFPEF) affects about half of all patients diagnosed with heart failure. The pathophysiological aspect of this complex disease state has been extensively explored, yet it is still not fully understood. Since the sympathetic nervous system is related to the development of systolic HF, we hypothesized that an increased sympathetic nerve activation (SNA) is also related to the development of HFPEF. This review summarizes the available literature regarding the relation between HFPEF and SNA. Electronic databases and reference lists through April 2014 were searched resulting in 7722 unique articles. Three authors independently evaluated citation titles and abstracts, resulting in 77 articles reporting about the role of the sympathetic nervous system and HFPEF. Of these 77 articles, 15 were included for critical appraisal: 6 animal and 9 human studies. Based on the critical appraisal, we selected 9 articles (3 animal, 6 human) for further analysis. In all the animal studies, isoproterenol was administered to mimic an increased sympathetic activity. In human studies, different modalities for assessment of sympathetic activity were used. The studies selected for further evaluation reported a clear relation between HFPEF and SNA. Current literature confirms a relation between increased SNA and HFPEF. However, current literature is not able to distinguish whether enhanced SNA results in HFPEF, or HFPEF results in enhanced SNA. The most likely setting is a vicious circle in which HFPEF and SNA sustain each other.
    PLoS ONE 02/2015; 10(2):e0117332. DOI:10.1371/journal.pone.0117332 · 3.53 Impact Factor
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    ABSTRACT: Hypertensive cardiomyopathy is characterized by myocyte hypertrophy and interstitial fibrosis. The effects of renal denervation (RD) on the heart are poorly understood. New magnetic resonance imaging techniques (extracellular volume fraction) permit the quantitative assessment of myocardial fibrosis. Our aim was to study the effects of RD on myocardial fibrosis. Twenty-three patients with resistant hypertension undergoing RD and 5 resistant hypertensive controls were prospectively included. Cardiac magnetic resonance imaging at 1.5 T was performed before RD and at 6-month follow-up. Indexed left ventricular mass, septal extracellular volume fraction, and indexed absolute extracellular volume (a quantitative measure of extracellular matrix) were quantified. All data are reported as mean±SD deviation (median). Decreases in systolic (161.96±19.09 [160] versus 144.78±16.48 [143] mm Hg, P<0.0001) and diastolic (85.61±12.88 [83] versus 80.39±11.93 [81] mm Hg, P=0.018) blood pressures and in indexed left ventricular mass (41.83±10.20 [41.59] versus 37.72±7.44 [38.49] g/m(1.7), P=0.001) were observed at follow-up only in RD patients. No significant differences in extracellular volume were found (26.24±3.92% [26.06%] versus 25.74±4.53% [25.63%], P=0.605). A significant decrease in absolute extracellular volume was observed after 6 months in RD patients exclusively (10.36±2.25 [10.79] versus 9.25±2.38 [9.79] mL/m(1.7), P=0.031). This effect was observed independently of blood pressure reduction. RD significantly decreases left ventricular mass, while extracellular volume remains stable. Our results suggest that the observed left ventricular mass decrease was due not exclusively to a reversion of myocyte hypertrophy but also to an additional reduction in collagen content, indicating interstitial myocardial fibrosis. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 10/2014; 3(6). DOI:10.1161/JAHA.114.001353 · 2.88 Impact Factor

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