Numaguchi K, Egashira K, Sakata M, Shimokawa H, Takeshita A
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Hypertens. 1996 Feb;14(2):183-9. doi: 10.1097/00004872-199602000-00006.
To determine whether opening of coronary vascular adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels is involved in the maintenance of resting coronary flow in hypertrophied hearts.
We examined the effects of glibenclamide, a selective inhibitor of KATP channels, on basal coronary vascular tone in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Using a Langendorff system, the hearts from WKY rats and SHRs were isolated and perfused with oxygenated Krebs-Henseleit solution at a constant perfusion pressure of 60 and 100 mmHg respectively.
Basal coronary flow and myocardial oxygen consumption (MV02) were similar in SHRs and WKY rats. The percentage decreases in coronary flow with glibenclamide at graded doses were greater (P < 0.01) in SHRs than in WKY rats (n = 8), whereas the percentage decreases in MV02 with glibenclamide were similar in the two groups. The decreases in coronary flow caused by U46619 (a thromboxane A2-mimetic agent) were similar in SHRs and WKY rats (n = 4). The increase in coronary flow caused by pinacidil (a KATP opener) was greater in SHRs than in WKY rats; glibenclamide prevented the pinacidil-induced increase in coronary flow in both SHRs and WKY rats. There was a significant positive correlation between the glibenclamide-induced decrease in coronary flow and the degree of left ventricular hypertrophy (r = 0.54, P < 0.05).
Our results suggest that the basal opening state of coronary vascular KATP channels is activated to a greater extent in SHRs than WKY rats, which may contribute to the maintenance of basal myocardial perfusion in hypertrophied hearts.
确定冠状动脉血管腺苷三磷酸(ATP)敏感性钾(KATP)通道的开放是否参与肥厚心脏静息冠脉血流的维持。
我们研究了KATP通道的选择性抑制剂格列本脲对Wistar - Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)基础冠脉血管张力的影响。使用Langendorff系统,分别从WKY大鼠和SHR分离心脏,并在60和100 mmHg的恒定灌注压力下用含氧的Krebs - Henseleit溶液灌注。
SHR和WKY大鼠的基础冠脉血流和心肌耗氧量(MV02)相似。在SHR中,不同剂量格列本脲引起的冠脉血流降低百分比比WKY大鼠更大(P < 0.01)(n = 8),而两组中格列本脲引起的MV02降低百分比相似。U46619(一种血栓素A2模拟剂)引起的SHR和WKY大鼠冠脉血流降低相似(n = 4)。匹那地尔(一种KATP开放剂)引起的SHR冠脉血流增加比WKY大鼠更大;格列本脲可阻止匹那地尔引起的SHR和WKY大鼠冠脉血流增加。格列本脲引起的冠脉血流降低与左心室肥厚程度之间存在显著正相关(r = 0.54,P < 0.05)。
我们的结果表明,与WKY大鼠相比,SHR中冠脉血管KATP通道的基础开放状态被激活的程度更大,这可能有助于肥厚心脏基础心肌灌注的维持。