title: The differential effects of low and high doses of apelin through opioid receptors on the blood pressure of rats with renovascular hypertension.
abstract: The apelin/APJ system has an important role in the regulation of vascular tone and blood pressure. Opioid receptors (OPRs) are also important cardiovascular regulators and exert many of their effects by modulating the function of other G-protein-coupled receptors. The aim of this study was to analyze the interaction of apelin and the opioid system with respect to vascular responses to apelin in rats with renovascular hypertension (two-kidney, one clip (2K1C)). Homodynamic studies were carried out in 2K1C rats. Naloxone (a nonselective OPR inhibitor) or nor-binaltorphimine dihydrochloride (norBNI, a kappa OPR inhibitor) and signaling pathway inhibitors PTX (a Gi path inhibitor) and chelerythrine (a protein kinase C (PKC) inhibitor) were administered before apelin at 20 and 40 μg kg-1. Apelin at 20 and 40 μg kg-1decreased the systolic blood pressure by 15% and 20%, respectively (P<0.05). The pressure drop caused by apelin 20 was inhibited by naloxone, norBNI and PTX, but it was not affected by chelerythrine. The pressure drop caused by apelin 40 was augmented by naloxone and chelerythrine, and it was not affected by norBNI or PTX. The lowering effect of apelin 20 on blood pressure is exerted through OPRs and stimulation of Gi and PKC pathways. However, apelin 40 functions independently of OPRs, Gi and PKC. This dose-dependent differential effect of apelin may have potential clinical applications as opioids are currently used, and apelin has been introduced as a potential therapeutic agent in cardiovascular complications.
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Yeganeh-Hajahmadi
authors.affiliation: Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Najafipour
authors.affiliation: Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Rostamzadeh
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000073861:Apelin / Q000008:administration & dosage* / Q000627:therapeutic use*; D053119:Benzophenanthridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D000073861:Apelin; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C016299:chelerythrine; D011493:Protein Kinase C