[Effects of ATP-sensitive potassium channel opener iptakalim against ventricular remodeling and its mechanisms of endothelial protection].
OBJECTIVE
To study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.


METHODS
ISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).


RESULTS
Six weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).


CONCLUSIONS
Ipt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.
Guangxi Medical University, Nanning 530021, China.
Ming-Li
ML
Zhong
Hui
H
Wang
Hong-Min
HM
Zhou
Yan-Fang
YF
Zhang
Wen-Yu
WY
Cui
Chao-Liang
CL
Long
Lian
L
Duan
Hai
H
Wang
D000818:Animals; D019332:Endothelin-1 / Q000097:blood; D006439:Hemodynamics; D006909:Hydroxyproline / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D044062:Prostaglandins I / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects*
D019332:Endothelin-1; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D044062:Prostaglandins I; D007545:Isoproterenol; D006909:Hydroxyproline