신규 합성 $K_{ATP}$ 통로 개방제인 KR-31281, KR-31282 및 KR-31299의 흰쥐 적출 허혈 심장 및 비마취 흰쥐에 대한 심장보호 및 혈압강하 작용

Cardioprotective and Antihypertensive Effects of KR-31281, KR-31282 and KR-31299, Newly Synthesized $K_{ATP}$ Openers, in Conscious Rats and Isolated Ischemic Rat Hearts

Cardiac and antihypertensive effects of BMS-180448, a cardiac-selective ATP-sensitive potassium channel opener, and its newly synthesized derivatives KR-31281, KR-31282 and KR-31299 were evaluated in isolated perfused rat hearts (25 min global ischemia/30 min reperfusion) and conscious rats. Three new compounds $(10\;{\mu}M)$ induced positive inotropism as evidenced by increased LVDP (left ventricular developed pressure) and RPP (Rate-Pressure Product) in nonischemic rat heart. HR-31299 increased CF (coronary flow) and HR (heart rate) but the other two had no effects. KR-31282, KR-31281 and HR-31299 had a tendency to increase reperfusion LVDP and RPP compared with vehicle, while the latter two significantly reduced reperfusion EDP with a tendency to inclose TTC (time to contracture). All three KR-compounds had very weak effects on MBP and HR in conscious rats. These results indicate that KR-31281 and HR-31299 may have some cardioprotective effects, although weaker than BMS-180448, and their mode of action different from that of BMS-180448, despite the similarity in major structural moeity.