Rostamzadeh Farzaneh, Najafipour Hamid, Yeganeh-Hajahmadi Mahboobeh, Joukar Siyavash
Neuroscience Research Center, Institute of Neuropharmacology and Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Clin Exp Pharmacol Physiol. 2018 Feb;45(2):187-197. doi: 10.1111/1440-1681.12860. Epub 2017 Nov 28.
Apelin receptors (APJ) cross-talk with other G-protein-coupled receptors. However, the role of APJ interaction with opioid receptors (OPR) on the cardiovascular effects of apelin in hypertension is not clear. Renovascular hypertension was induced by placing a Plexiglas clip on the left kidney of rats. After 16 weeks, F13A (an APJ antagonist), naloxone (a general OPR inhibitor), and nor-binaltorphimine dihydrochloride (nor-BNI; a selective inhibitor of KOR) were given prior to injections of apelin at doses of 40 and 60 μg/kg. The arterial systolic/diastolic blood pressure and left ventricular contractility responses were then evaluated. The arterial systolic/diastolic blood pressure in sham and 2K1C rats was 110/71 mm Hg and 171/124 mm Hg, respectively. The hypotensive effects of apelin at both doses were inhibited by F13A and naloxone. Nor-BNI completely inhibited the effects of apelin 40 on arterial pressure, and decreased the effects of 60 μg/kg. KOR inhibition also prevented the compensation for the decrease in the left ventricle +dp/dt max and -dp/dt max caused by apelin 60. The simultaneous inhibition of OPR and APJ reduced arterial pressure and increased cardiac contractility. Findings showed that the OPR, particularly KOR, mediate the inotropic, lusitropic, and depressor effects of apelin. The interaction of the OPR and APJ augments the inotropic and vasodepressor effects of apelin. This interaction may have potential clinical applications in cardiac failure since opioids are currently used in the treatment of myocardial infarction and stroke, and apelin has been introduced as a potential therapeutic agent in cardiovascular complications.
阿片肽受体（APJ）与其他G蛋白偶联受体存在相互作用。然而，在高血压中，APJ与阿片受体（OPR）相互作用对阿片肽心血管效应的作用尚不清楚。通过在大鼠左肾放置有机玻璃夹诱导肾血管性高血压。16周后，在注射剂量为40和60μg/kg的阿片肽之前，分别给予F13A（一种APJ拮抗剂）、纳洛酮（一种通用的OPR抑制剂）和盐酸去甲二氢吗啡酮（nor-BNI；一种κ阿片受体（KOR）选择性抑制剂）。然后评估动脉收缩压/舒张压和左心室收缩力反应。假手术组和二肾一夹（2K1C）大鼠的动脉收缩压/舒张压分别为110/71 mmHg和171/124 mmHg。F13A和纳洛酮抑制了两种剂量阿片肽的降压作用。Nor-BNI完全抑制了40μg/kg阿片肽对动脉血压的作用，并减弱了60μg/kg阿片肽的作用。抑制KOR也阻止了对阿片肽60引起的左心室+dp/dt max和-dp/dt max降低的代偿。同时抑制OPR和APJ可降低动脉血压并增强心脏收缩力。研究结果表明，OPR，尤其是KOR，介导了阿片肽的正性肌力、舒张期和降压作用。OPR与APJ的相互作用增强了阿片肽的正性肌力和血管舒张降压作用。由于目前阿片类药物用于治疗心肌梗死和中风，而阿片肽已被引入作为心血管并发症的潜在治疗药物，这种相互作用在心力衰竭中可能具有潜在的临床应用价值。
