Angiotensin II type 1 receptor blockade abolishes specific K-ATP channel gene expression in rats with myocardial ischemia

The cardiac ATP-sensitive potassium (K-ATP) channel is potentially composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit an d the cardiac type of sulfonylurea receptor (SUR2A). We reported that cardi ac Kir6.1 mRNA and protein are specifically upregulated in the non-ischemic as well as the ischemic regions in rats with myocardial ischemia, suggesti ng that humoral and/or hemodynamic factors are responsible for this regulat ion. In the present study, pretreatment with TCV-116, an angiotensin (Ang) II type 1 receptor antagonist, completely inhibited the upregulation of Kir 6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 min of coronary artery occlusion followed by 24 h of reperfusion; wherea s pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, p artly inhibited this upregulation. Except for rats pretreated with TCV-116, Kir5.1 mRNA levels were positively correlated with those for brain natriur etic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not el evated in rats with control myocardial ischemia compared with sham rats. Th us, the stress-related induction of cardiac Kir6.1 mRNA and protein express ion under myocardial ischemia is inhibited by pretreatment with an AT1 anta gonist, but also in part by an ACE inhibitor, suggesting that activation of local renin-angiotensin system may play a role. (C) 2000 Academic Press.