title: Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.
abstract: Increasing evidence suggests that angiotensin II (AngII) acts as a modulator for ventricular remodeling after myocardial infarction. Using competitive reverse-transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we examined the regulation of AngII type 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in the infarcted rat heart as well as the effects of AngII receptor antagonists. AT1a-R mRNA levels were increased in the infarcted (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after myocardial infarction as compared with those in sham-operated controls, whereas AT1b-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in the control. The transcription rates for AT1a-R and AT2-R genes, determined by means of a nuclear runoff assay, were significantly increased in the infarcted heart. The AngII receptor numbers were elevated (from 12 to 35 fmol/mg protein) in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2- and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions in the infarcted heart together with a decrease in blood pressure, whereas therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure. Neither AT1-R nor AT2-R antagonists affected the infarct sizes. These results demonstrated that myocardial infarction causes an increase in the gene transcription and protein expression of cardiac AT1a-R and AT2-R, whereas the AT1b-R gene is unaffected, and that therapy with an AT1-R antagonist, but not with an AT2-R antagonist, is effective in reducing the increased expression of AngII receptor subtypes induced by myocardial infarction.
authors: Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors: Y
authors: Y
authors: Nio
authors: H
authors: H
authors: Matsubara
authors: S
authors: S
authors: Murasawa
authors: M
authors: M
authors: Kanasaki
authors: M
authors: M
authors: Inada
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000737:chemistry; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000378:metabolism*; D009929:Organ Size; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D013777:Tetrazoles; D014158:Transcription, Genetic
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C073402:PD 123319; C077793:candesartan cilexetil