Current views on mechanisms of vasodilation in response to ischemia and hypoxia

Abstract

Myocardial function (and thus life) is entirely dependent on sufficient O₂ supply. Therefore, this supply is extremely well regulated via a refined system of interacting mechanisms. These have been subject to extensive research for more than 100 years. Surprisingly, remarkable dispute still arises among scientists concerning the factors and mechanisms involved in this regulatory system.

During ischemia, myocardial cells have been shown to release vasoactive metabolites (eg, H⁺ and K⁺ ions, lactic acid, adenosine, and others), which cause spontaneous coronary dilation. On the other hand claims have been made that the endothelium itself could play a key role in hypoxic/ischemic vasodilation by releasing endothelium-derived relaxant factor (EDRF) (NO = nitric oxide) and other still partially unspecified vasoactive substances (eg, prostaglandins). Furthermore, it has been discussed that intravascular O₂ tension (pO₂) itself would exert a direct effect upon endothelial and/or vascular smooth muscle cells and thus produce per se a local reflectory vasodilation. In contrast, the intravascular CO₂ tension has also been shown to act upon coronary vascular resistance during myocardial ischemia. Recently, hints have been made about the membrane potential of arterial smooth muscle cells as a key factor in hypoxia/ischemia vasodilation. However, during hypoxia and metabolic inhibition, the membrane potential seems to be modulated primarily by the action of adenosinetriphosphate-dependent (ATP) potassium channels (K⁺ _ATP channels).

In conclusion, a number of factors contribute to ischemia/hypoxia-induced vasodilation. The present review contrasts recent findings on ATP-dependent K⁺ channels with other experimental evidence concerning other mechanisms involved in hypoxic/ischemic vasodilation.