M. Akao et al., Angiotensin II type 1 receptor blockade abolishes specific K-ATP channel gene expression in rats with myocardial ischemia, J MOL CEL C, 32(12), 2000, pp. 2239-2247
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.