scholarly journals Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

2021 ◽  
Author(s):  
Lukas Dehe ◽  
Mohammed Shaqura ◽  
Michael Nordine ◽  
Helmut Habazettl ◽  
Petra von Kwiatkowski ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Wistar Rats ◽  
Volume Overload ◽  
Left Ventricular ◽  
Endogenous Opioid ◽  
Kappa Opioid ◽  
Receptor Mrna ◽  
Naltrexone Treatment

Abstract Purpose Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure. Methods Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls. Results In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls. Conclusion Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.

kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury

1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Neurological Outcome ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonist ◽  
Cellular Bioenergetics

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.

Involvement of kappa-opioid receptors in peripheral response to nerve stimulation in kappa-opioid receptor knockout mice

2002 ◽  
Vol 22 (4) ◽  
pp. 233-239 ◽  
Author(s):  
D. Mitolo-Chieppa ◽  
L. Natale ◽  
F. L. Marasciulo ◽  
G. De Salvatore ◽  
C. I. Mitolo ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Nerve Stimulation ◽  
Knockout Mice ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid

Detection of opioid receptor mRNA by RT-PCR reveals alternative splicing for the δ- and κ-opioid receptors

1997 ◽  
Vol 48 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Claire Gavériaux-Ruff ◽  
Jean Peluso ◽  
Katia Befort ◽  
Frédéric Simonin ◽  
Christelle Zilliox ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Rt Pcr ◽  
Receptor Mrna

Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

2011 ◽  
Vol 121 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Jan Benes ◽  
Ludmila Kazdova ◽  
Zdenek Drahota ◽  
Josef Houstek ◽  
Dasa Medrikova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Glycogen Synthesis ◽  
Volume Overload ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Term Survival ◽  
Palmitate Oxidation ◽  
Substrate Metabolism ◽  
Mitochondrial Functions

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. The antihyperglycaemic drug MET (metformin) affects substrate metabolism, and its use might be associated with improved outcome in diabetic HF. The aim of the present study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Volume-overload HF was induced in male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized to placebo/MET (300 mg·kg−1 of body weight·day−1, 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6–12/group) in advanced HF stage (week 21). A separate cohort served for survival analysis (n=10–90/group). The ACF group had marked cardiac hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) and lung weight confirming decompensated HF, increased circulating NEFAs (non-esterified ‘free’ fatty acids), intra-abdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triacylglycerol (triglyceride) content and attenuated myocardial 14C-glucose and 14C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels (2.2±0.7 μg/ml). In conclusion, MET-induced enhancement of myocardial fatty acid oxidation had a neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF.

Abstract 3292: Cardiac Dysfunction Induced By Chronic Restrain Stress Is Mediated By Opioid Receptors

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jinping Gao ◽  
Chu C Chua ◽  
Deling Yin ◽  
Hong Wang ◽  
Ronald C Hamdy ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Chronic Stress ◽  
Opioid Receptors ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Opioid Antagonist ◽  
Stroke Work ◽  
Ventricular Performance ◽  
Major Health Problem ◽  
Stressed Group

Psychological and physical stressors are a major health problem in our society. The effect of chronic stress on myocardial function has not been assessed. Our hypothesis is that chronic stress induces cardiac dysfunction and that its effect is mediated by activation of opioid receptors (OPR). Six week-old male ICR mice were restrained for 12 h with no food and water. This was followed by 12 h of rest with food and water provided ad labium. Unstressed (control) mice were kept in the original cage and were not given food and water during the stress period of the experimental group. Left ventricular performance was analyzed in mice anesthetized with 2% isoflurane using an ARIA pressure-volume conductance system (Millar Instruments). Our studies demonstrated for the first time that cardiac function was significantly depressed in restrained mice, as evidenced by a significant decrease in body weight (9%), heart rate (21%), stroke volume (38%), cardiac output (52%), ejection fraction (27%) and preload recruitable stroke work (43%). Systolic function (control vs. stressed group) (P<0.05), was 88 ± 2.2 vs. 68 ± 2.8 mmHg for end-systolic pressure, 6.1 ± 0.15 vs. 7.6 ± 0.15 μl for end-systolic volume, and 11,471 ± 913 vs. 5,860 ± 761 mmHg/s for +dP/dt. Diastolic function (control vs. stressed group) (P<0.05), was 2.9 ± 0.3 vs. 5.0 ± 0.5 mmHg for end-diastolic pressure, 17.1 ± 0.4 vs. 14.4 ± 0.5 μl for end-diastolic volume, 7,678 ± 419 vs. 4,195 ± 358 mmHg/s for -dP/dt, and 7.1 ± 0.5 vs. 10.8 ± 1.1 ms for tau (time constant of isovolumic relaxation). Peripheral vascular resistance (Ea) increased from 7.7 ± 0.2 in the control group to 9.8 ± 0.7 mmHg/μ l in the stressed group (P<0.05). Administration of an opioid antagonist naltrexone (8 mg/kg, i.p.) during each cycle of stress completely restored the cardiac function of stressed mice. Naltrexone alone had no effect on cardiac function in unstressed mice. These intriguing data suggest that opioid receptors are involved in the chronic stress-induced cardiac dysfunction and that treatment with an opioid antagonist can prevent this cardiac dysfunction.

EVIDENCE FOR A CENTRAL OPIOID CONTROL OF RUMINATION

1984 ◽  
Vol 64 (5) ◽  
pp. 13-15 ◽  
Author(s):  
Y. RUCKEBUSCH ◽  
TH. BARDON
Keyword(s):  
Key Words ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Receptor Agonists ◽  
Opioid Agonists ◽  
Reflex Control ◽  
Opioid Receptor Agonists

Intravenous adrenaline induced reticular extracontractions and rumination within 26 sec in hay-fed, and 184 sec in cube-fed sheep. Regardless of diet, pretreatment with cerebroventricular infusion of kappa-opioid-receptor agonists enhanced this reflex. Control of rumination may involve multiple opioid-receptors, since inhibition of the reflex occurred after mu- and delta-opioid-agonists. Key words: Sheep, rumination, opioid-peptides

Distinct Distributions of Mu, Delta and Kappa Opioid Receptor mRNA in Rat Brain

1994 ◽  
Vol 205 (2) ◽  
pp. 1438-1444 ◽  
Author(s):  
S.R. George ◽  
R.L. Zastawny ◽  
R. Brionesurbina ◽  
R. Cheng ◽  
T. Nguyen ◽  
...  
Keyword(s):  
Rat Brain ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Receptor Mrna

scholarly journals Molecular cloning of a rat κ opioid receptor reveals sequence similarities to the μ and δ opioid receptors

1993 ◽  
Vol 295 (3) ◽  
pp. 625-628 ◽  
Author(s):  
Y Chen ◽  
A Mestek ◽  
J Liu ◽  
L Yu
Keyword(s):  
Adenylate Cyclase ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Brain Cdna Library ◽  
Inhibitory Coupling ◽  
Receptor Cdna ◽  
G Protein Coupled ◽  
Sequence Similarities

By screening a rat brain cDNA library using a cloned mu opioid receptor cDNA as probe, a clone was identified that is very similar to both the mu and delta opioid receptor sequences. Transient expression of this clone in COS-7 cells showed that it encodes a kappa opioid receptor, designated KOR-1, which is capable of high-affinity binding to kappa-selective ligands. Treatment of transfected cell membranes with bremazocine, a kappa-selective agonist, resulted in a 53% decrease in adenylate cyclase activity, indicating that this kappa opioid receptor displays inhibitory coupling to adenylate cyclase. Thus, one member from each of the three opioid receptor types, mu, kappa and delta, has been molecularly cloned. Analysis of sequence similarities among these opioid receptors, as well as between opioid receptors and other G-protein-coupled receptors, revealed regions of sequence conservation that may underlie the ligand-binding and functional specificities of opioid receptors.

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