Effects of methylprednisolone on hemodynamics and beta-adrenergic receptor signaling in rabbits with acute left ventricular failure.
Studies suggest that corticosteroids may restore the responsiveness to catecholamines in hypotensive patients. Since the significance of this promising intervention in congestive heart failure remains to be explored, we determined the effects of methylprednisolone, a potent activator of beta-adrenergic receptor signaling, on hemodynamics and beta-adrenergic receptor regulation in an animal model of heart failure. Acute left ventricular overloading was produced by aortic regurgitation (AR) in 22 Japanese white rabbits. Eleven animals received an intravenous administration of methylprednisolone (AR + PSL), while 11 received saline (AR + C) for 1 week. A sham operation was performed on 10 other rabbits (S). There was no difference between the AR + C and AR + PSL groups in the decrease in aortic diastolic pressure immediately after the production of AR. The aortic diastolic pressure and regurgitant fractions were also similar in the two groups. The left ventricular end-diastolic and end-systolic dimensions were both larger, and the left ventricular end-diastolic pressure was higher in AR + C or AR + PSL than in S rabbits. Between the AR + C and AR + PSL, there were no differences in any of these variables. Cardiac output was lower in AR + C, but not in AR + PSL, than in S. Cardiac output in AR + PSL was significantly higher than in AR + C. The myocardial concentration of norepinephrine and the number of beta-adrenergic receptors were both lower in the AR + C and AR + PSL than in the S groups. The number of receptors in AR + PSL was higher than in AR + C. Maximal isoproterenol-stimulated adenylyl cyclase activity was similar in the AR + C and AR + PSL groups. Results suggest methylprednisolone yielded some benefits, including an increase in cardiac output and in total beta-adrenergic receptor number, in this animal model of heart failure.
Nishimura
H
H
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Yoshikawa
T
T
Kobayashi
N
N
Anzai
T
T
Nagami
K
K
Handa
S
S
Ogawa
S
S
D000818:Animals; D001022:Aortic Valve Insufficiency / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D008775:Methylprednisolone / Q000494:pharmacology*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology*; D017725:Ventricular Pressure / Q000187:drug effects
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D008775:Methylprednisolone