Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats.
Acute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system because of mineralocorticoid receptor activation, as morphine increases plasma corticosterone concentrations. Morphine-dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalised in morphine-dependent rats treated with spironolactone (50 mg/kg/day) from days 14-21. These results suggest that morphine dependence induces ventricular remodelling and increased oxidative stress that can be prevented by the mineralocorticoid receptor antagonist, spironolactone.
Medical Plants Research Centre, Shahrekord University of Medical Sciences, Shahrekord, Iran. mesripour@skums.ac.ir
Azadeh
A
Mesripour
Abishek
A
Iyer
Lindsay
L
Brown
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018613:Microscopy, Confocal; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D008315:Malondialdehyde; D009020:Morphine