Cardiac beta-adrenergic signaling pathway alteration in isoproterenol-induced cardiac hypertrophy in male Sprague-Dawley rats.
Isoproterenol was continuously administered to rats at a rate of 2.5 microg/kg/min for 7 days via subcutaneously implanted osmotic minipumps. This treatment induced cardiac hypertrophy with increases in heart rate and systolic blood pressure. Beta-adrenoceptor (beta-AR) density decreased in hypertrophied hearts, but the affinity for 125I-cyanopindolol did not change. The beta-AR density decrease did not accompany the change in expression of beta1-AR mRNA. In hypertrophied hearts, adenylyl cyclase activities in the steady state, and stimulated with isoproterenol, forskolin, and manganese, decreased but there was no change in the expression of adenylyl cyclase type V mRNA. The results suggest that beta-AR downregulation and adenylyl cyclase desensitization in isoproterenol-induced cardiac hypertrophy are caused by post-transcriptional changes.
Hakamata
N
N
Department of Medicine I, National Defense Medical College, Tokorozawa, Saitama, Japan.
Hamada
H
H
Ohsuzu
F
F
Nakamura
H
H
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D002395:Catecholamines / Q000502:physiology; D018076:DNA, Complementary / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D018076:DNA, Complementary; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D000262:Adenylyl Cyclases; D007545:Isoproterenol