Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure
| Autor: | Kara Garrott, Xin Wang, Mary Kate Dwyer, David Mendelowitz, Matthew W. Kay, Edmund Cauley, Sarah Kuzmiak-Glancy, Jhansi Dyavanapalli |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Physiology 030204 cardiovascular system & hematology Oxytocin Left ventricular hypertrophy Muscle hypertrophy Rats Sprague-Dawley Contractility 03 medical and health sciences 0302 clinical medicine Invited Editorials Physiology (medical) Internal medicine Heart rate medicine Animals Heart Failure Neurons business.industry Myocardium Isoproterenol Heart medicine.disease Myocardial Contraction stomatognathic diseases Endocrinology Rate pressure product Heart failure Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cardiovascular Research. 113:1318-1328 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvx084 |
| Popis: | Aims A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Methods and results Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Conclusions Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were significantly higher in TAC + OXT compared with TAC animals. HR sensitivity, but not contractile sensitivity, to β-adrenergic stimulation was improved in TAC + OXT hearts. |
| Databáze: | OpenAIRE |
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