Myocardial postconditioning is lost in vascular nitrate tolerance

Area of Science:

• Cardiology
• Pharmacology
• Molecular Biology

Background:

• Organic nitrates are crucial for treating ischemic heart disease but are limited by vascular nitrate tolerance.
• Previous research indicated that vascular nitrate tolerance attenuates the cardioprotective effects of preconditioning.
• The impact of nitrate tolerance on ischemic postconditioning (IPost) and its underlying mechanisms remained unclear.

Purpose of the Study:

• To investigate whether vascular nitrate tolerance affects the infarct size-limiting efficacy of IPost in the myocardium.
• To determine if survival kinase activation is involved in the molecular mechanism of IPost, with or without nitrate tolerance.

Main Methods:

• Male Wistar rats were treated with nitroglycerin to induce vascular nitrate tolerance.
• Isolated hearts underwent 30 minutes of coronary occlusion followed by 120 minutes of reperfusion, with or without IPost.
• Levels of phosphorylated ERK 1/2, Akt, and endothelial nitric oxide synthase were measured.

Main Results:

• IPost significantly reduced infarct size in non-tolerant hearts compared to ischemia/reperfusion alone.
• IPost failed to decrease infarct size in nitrate-tolerant rat hearts.
• No significant differences in the phosphorylation of survival kinases were observed between groups.

Conclusions:

• Vascular nitrate tolerance interferes with the infarct size-limiting effect of IPost.
• The activation of survival kinases is not essential for the molecular mechanism of IPost and is unaffected by nitrate tolerance.