Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
| Autor: | Petra von Kwiatkowski, Helmut Habazettl, Mehdi Shakibaei, Helena Schluchter, Michael Schäfer, Michael Nordine, Shaaban A. Mousa, Sascha Treskatsch, Lukas Dehe, Mohammed Shaqura |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Neurohumoral medicine.drug_class Narcotic Antagonists Volume overload Nerve Tissue Proteins 030204 cardiovascular system & hematology Contractility Naltrexone 03 medical and health sciences Ventricular Dysfunction Left 0302 clinical medicine Opioid receptor Internal medicine medicine Animals Pharmacology (medical) Myocytes Cardiac Rats Wistar Opioid peptide Endogenous opioid Pharmacology business.industry Angiotensin II Routine Article Hemodynamics Water Intoxication General Medicine medicine.disease Rats Opioids Disease Models Animal Endocrinology Treatment Outcome Opioid Heart failure Heart Function Tests Receptors Opioid Cardiac dysfunction Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cardiovascular Drugs and Therapy |
| ISSN: | 1573-7241 0920-3206 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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