Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart
- 1 February 2010
- journal article
- research article
- Published by Wolters Kluwer Health in Hypertension
- Vol. 55 (2), 270-276
- https://doi.org/10.1161/hypertensionaha.109.142042
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-γ, 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.Keywords
This publication has 35 references indexed in Scilit:
- Cardiac Mast Cells Mediate Left Ventricular Fibrosis in the Hypertensive Rat HeartHypertension, 2009
- Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix RemodelingHypertension, 2006
- Survival Benefits of Different Antiadrenergic Interventions in Pressure Overload Left Ventricular Hypertrophy/FailureHypertension, 2006
- Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusionJCI Insight, 2006
- Sympathectomy or Doxazosin, But Not Propranolol, Blunt Myocardial Interstitial Fibrosis in Pressure-Overload HypertrophyHypertension, 2005
- The autonomic nervous system of the human heart with special reference to its origin, course, and peripheral distributionBrain Structure and Function, 2005
- Hypertensive Myocardial Fibrosis and Diastolic DysfunctionHypertension, 2004
- Catecholamine Influences and Sympathetic Neural Modulation of Immune ResponsivenessAnnual Review of Pharmacology and Toxicology, 1995
- Neuropeptides Contained in Peripheral Cardiovascular NervesClinical and Experimental Hypertension. Part A: Theory and Practice, 1984
- Pinacyanol Erythrosinate as A Stain for Mast CellsStain Technology, 1952