title: Angiotensin II type 1 receptor blockade abolishes specific K(ATP)channel gene expression in rats with myocardial ischemia.
abstract: The cardiac ATP-sensitive potassium (K(ATP)) channel is potentially composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the cardiac type of sulfonylurea receptor (SUR2A). We reported that cardiac Kir6.1 mRNA and protein are specifically upregulated in the non-ischemic as well as the ischemic regions in rats with myocardial ischemia, suggesting that humoral and/or hemodynamic factors are responsible for this regulation. In the present study, pretreatment with TCV-116, an angiotensin (Ang) II type 1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 min of coronary artery occlusion followed by 24 h of reperfusion; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. Except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared with sham rats. Thus, the stress-related induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia is inhibited by pretreatment with an AT1 antagonist, but also in part by an ACE inhibitor, suggesting that activation of local renin-angiotensin system may play a role.
authors: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
authors: M
authors: M
authors: Akao
authors: T
authors: T
authors: Sakurai
authors: M
authors: M
authors: Horie
authors: H
authors: H
authors: Otani
authors: M
authors: M
authors: Takano
authors: I
authors: I
authors: Kouchi
authors: T
authors: T
authors: Murakami
authors: S
authors: S
authors: Sasayama
mesh_terms: D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018076:DNA, Complementary; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D012313:RNA; D000803:Angiotensin I; D017706:Lisinopril; C077793:candesartan cilexetil