Assessment of endothelium-dependent vasodilation in the clinic: what endothelial factor are we studying?

Objective . To study the contribution of the main endothelial vasodilators using different functional tests. Design and methods . Blood flow in the microvessels of the forearm skin was assessed in 30 healthy volunteers (20-21 years) using high-frequency Doppler ultrasound. Three functional tests were performed: iontophoresis with acetylcholine, a test with reactive hyperemia and a temperature test with local heating of the forearm skin to 42 °C. To analyze the mechanisms of endothelium-dependent vasodilation we carried out iontophoresis of vasoactive substances: L-Nitro-Arginine Methyl Ester (L-NAME) — inhibitor of endothelial NO synthase (eNOS), tetraethylammonium (TEA) — inhibitor of endothelial hyperpolarizing factor (EDHF), diclofenac sodium — inhibitor of cyclooxygenase (COX). Results . During the test with acetylcholine was characterized by a rapid increase in the volume rate of blood flow for 2 minutes, from 4 minutes there was a slow decrease in the volume rate of blood flow. The blockade of nitric oxide and prostacyclin led to a slowdown in blood flow growth and the blockade of EDHF to accelerate the recovery of the reaction of microvessels to acetylcholine. In postocclusion test changes in blood flow occur only under blockade of nitric oxide, while the blockade of EDHF and prostacyclin showed no effect on reactive hyperemia. Similar results were obtained by local heating of the skin. Conclusions. Nitric oxide plays a leading role in all tests, including local heat test and flow-mediated dilation. Endothelial hyperpolarizing factor is significant only in the mechanism of acetylcholine-induced vasodilation.