Effect of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Type 1 Receptor Antagonist on Metabolism and Contraction in Ischemia-Reperfused Rabbit Heart

Abstract

The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat and/or angiotensin II type 1 (AT1) receptor antagonist, CV-11974 on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, postischemic reperfusion of 60min was carried out. Temocaprilat and/or CV-11974 were administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: group I consisted of controls, group II was perfused with temocaprilat (10(-6)mol/L), group III was perfused with CV-11974 (10(-6)mol/L), and group IV was perfused with temocaprilat (10(-6)mol/L) in combination with CV-11974 (10(-6) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with group I. Group IV also showed a more pronounced significant (p<0.01) inhibition of the overshoot of PCr during reperfusion compared with group I. Groups II, III and IV showed a significant (p<0.05) inhibition of the decrease in ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) compared with group I (45+/-3%). Groups II and IV showed a significant (p<0.05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared with group I (71+/-3%) and group II (73+/-2%). Group IV showed no more significant recovery in ATP than group III. There were no differences in LVDevP, LVEDP and coronary flow among these groups. In conclusion, temocaprilat in combination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.

Role of Cardiac ATP-Sensitive K+ Channels Induced by Angiotensin II Type 1 Receptor Antagonist on Metabolism, Contraction and Relaxation in Ischemia-Reperfused Rabbit Heart.

“…The 31 P-NMR spectra were recorded with a JNM-GX 400 FT NMR spectrometer (JEOL, Tokyo, Japan) operating at 161.7 MHz. The spectral parameters were: 45°pulse, 1.0 s intervals, 300 transients (5 min), 16,384 data points (8,192 sampling points, zero filling), 10,000 Hz sweep width, and line broadening of 20 Hz. Quantitative analysis was performed using the relative intensities of the -ATP, PCr (creatine phosphate), and Pi (inorganic phosphate) peaks.…”

“…6 Angiotensin II type 1 (AT1) receptor antagonists have the cardioprotective effect on ischemia-reperfusion injury. 7,8 And also, AT1 receptor antagonists have been shown to involve AT2 receptor activation and the subsequent action of bradykinin. 9 Recent evidence suggests that the adenosine triphosphate-sensitive K + (KATP) channels are mainly involved in effectors of cardioprotection against ischemia-reperfusion.…”

Does Angiotensin Converting Enzyme Inhibitor Protect the Heart in Cardiac Surgery? From Laboratory to Operating Room: Clinical Application of Experimental Study

“…ACE inhibitors protect not only in the presence of myocardial hypertrophy regression [5,27], but also in its absence [28]. They also show protective effects against ischemia/reperfusion injury such as ventricular dysfunction and arrhythmias [30,31].…”

Effects of an HMG-CoA Reductase Inhibitor in Combination with an ACE Inhibitor or Angiotensin II Type 1 Receptor Antagonist on Myocardial Metabolism in Ischemic Rabbit Hearts

“…Recent studies have suggested that HMG-CoA reductase inhibitors activate endothelial nitric oxide synthase (eNOS) independently of its effects on lipids (4,5). The renin-angiotensin system (RAS) is activated upon acute myosion injury in rabbit hearts (13). While ACE inhibitors have been shown to activate bradykinin, bradykinin enhances accumulation of endothelial nitric oxide (NO)/cyclic GMP (14).…”