Key Points
- To determine whether the cardioprotective effects of the ACE inhibitor ramiprilat against myocardial ischemia/reperfusion injury are mediated by kinin-stimulated release of prostaglandins and nitric oxide.
- Subjected Lewis inbred rats to 30 minutes of left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion.
- Administered vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan immediately before reperfusion.
- Evaluated infarct size and reperfusion arrhythmias following pretreatment with Hoe 140 (kinin receptor antagonist), L-NAME (nitric oxide synthase inhibitor), or indomethacin (cyclooxygenase inhibitor).
- Ramiprilat significantly reduced infarct size as a percentage of the area at risk from 79 ± 3% in controls to 49 ± 4% (P < .001), whereas losartan had no significant effect (74 ± 6%, P = NS).
- Pretreatment with Hoe 140, L-NAME, or indomethacin completely abolished the reduction in infarct size and the suppression of ventricular arrhythmias provided by ramiprilat.
Structured PICO
Does ramiprilat reduce infarct size in a rat model of myocardial ischemia/reperfusion injury?
PPopulationLewis inbred rats subjected to 30 minutes of left anterior descending coronary artery occlusion
IInterventionRamiprilat administered immediately before reperfusion
OOutcomeInfarct size as a percentage of the area at risksurrogate
The cardioprotective effects of ACE inhibitors against ischemia/reperfusion injury are mediated by a kinin-prostaglandin-nitric oxide pathway rather than angiotensin II inhibition.