Effect of Enalapril and Nitroglycerin on Reperfusion Arrythmias in Spontaneous Hypertensive Rats.

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It has been reported that the free radical is the major couse of reperfusion arrhythmias and that captopril, an angiotensin-converting enzyme inhibitor (ACE-I) with an SH radical, is useful in preventing reperfusion arrhythmias. However, recently it has been suggested that not only ACE-I with an SH radical, but also ACE-I without an SH radical has a preventative effect on reperfusion arrhythmias, and that these effects might be due to a decrease of the after load or the suppression of sympathetic tones. On the other hand, the role of hypertensive cardiac hypertrophy on reperfusion arrhythmia is not clear yet. In the present study, we attempted to determine the effect of enalapril, an ACE-I without an SH radical, on reperfusion arrhythmias in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) considering changes in blood pressure (BP), and also the effect of nitroglycerin (NTG) on the decreasing effect of pre- and after loads on reperfusion arrhythmias.<BR>Method: The coronary arteries of the rats under anesthesia by ether respiration were ligated by the Selye method. The rats were monitored by limb leads ECGs. Five minutes later, coronary arteries were united and reperfused. The reperfusion arrhythmias were compared between the SHRs and WKYs. Then the effects of two doses (0. 4 mg and 4. 0 mg) of enalapril, and a dose of NTG (0. 5 mg) were investigated in the SHRs. The changes of the active potential and activation time with enalapril were compared with nitroglycerin insections of the SHRs left ventricular papillar muscle in Tyrode solution saturated by oxygen.<BR>Results: The duration per rat of the total continuous ventricular tachycardia (VT) was: 1) 23. 3, 2) 179. 1, 3) 46. 3, 4) 57. 3 and 5) 38. 8 seconds in 1) WKY without any drugs, 2) SHR without any drugs, 3) SHR with NTG, 4) SHR with enalapril of 4. 4 mg and 5) SHR with enalapril of 4. 0 mg, respectively. The duration per rat of the total continuous ventricular fibrillation (VF) was 1) 0.5, 2) 61. 3, 3) 48, 4) 1. 3, 5) 5. 6 seconds, respectively. The effect of these drugs on BP were 40 mmHg in SHR with enalapril of 0.4 mg; 29 mmHg (poor responder) in SHR with enalapril of 4.0 mg; 75 mmHg (good responder) in SHR with enalapril of 4.0 mg; 15 mmHg in WKY; 19 mmHg in SHR with NTG.<BR>Enalapril at 4.0 mg had the effect of both decreasing BP and suppressing VT and VF after reperfusion. However, enalapril at 0. 4 mg showed only a slight suppression of BP, VT and VF. This is more remarkable in the SHR than in the WKY. The active potential duration of 70% with enalapril extended from 42 to 48 seconds, respectively, but there was no extension with nitroglycerin.<BR>Conclusion: 1) Frequency and duration of VT and VF in the SHR were more frequent longer than those in the WKY. 2) Enalapril of a larger dose (4.0 mg) produced a decrease in BP and a suppression of VT and VF, especially, in the SHR. 3) Smaller dosesenalapril (0.4 mg) had little effect on BP and arrhythmias. 4) NTG produced a decrease BP and a suppression of VT. 5) NTG did not extend APD 70, but enalapril did. 6) From these observation, it is suggested that the after load is one of the mechanisms of reperfusion VT and the chemical change is one of the mechanisms of reperfusion VF.
一般社団法人日本臨床薬理学会の論文

Effect of Enalapril and Nitroglycerin on Reperfusion Arrythmias in Spontaneous Hypertensive Rats.

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