Role of Endothelium in Oscillatory Contractile Responses to Various Receptor Agonists in Isolated Small Mesenteric and Epicardial Coronary Arteries

Abstract

Employing the isometric tension recording method, we studied the role of endothelium or endothelium-derived relaxing factor (EDRF) in the generation of rhythmic oscillations observed in contractile responses to various receptor agonists in isolated rabbit small mesenteric and epicardial coronary arteries. Norepinephrine (NE, 0.1-10 μM) generated oscillatory contraction in endothelium-intact strips from the mesenteric arteries. Similarly, acetylcholine (ACh, 10 μM), histamine (10 μM) and serotonin (10 μM) generated oscillatory contraction in endothelium-intact strips from the coronary arteries. These agonistinduced oscillations in both arteries were consistently eliminated by either endothelial denudation or EDRF pathway inhibitors including N^G-nitro L-arginine (30 and 100 μM), oxyhemoglobin (3 and 10 μM) and methylene blue (3 and 10 μM). In contrast, EDRF releasers such as ACh or A23187 augmented the oscillations in the endothelium-intact strips. SNP (0.03 - 30 μM) failed to generate oscillations in NE (10 μM)-preconstricted endothelium-denuded strips from the mesenteric arteries. In conclusion, these agonist-induced oscillations are probably mediated through EDRF. The inability of SNP to generate oscillations suggests the obligatory role of the endothelium in generation of the oscillations. The oscillatory release of EDRF by endothelial cells may be responsible for generation of the oscillations.