Endothelium-Dependent Responses in Small Human Mesenteric Arteries

A. TØTTRUP, K. KRAGLUND

Department of Surgery L, University Hospital of Aarhus, Amtssygehuset, Aarhus, Denmark

Received April 23, 2003
Accepted July 14, 2003



Summary
The aim of the present study was to investigate the endothelial function in human mesenteric arteries with specific reference to defining the role of endothelium-derived nitric oxide (EDNO) and the endothelium-derived hyperpolarizing factor (EDHF). Isolated segments of small human mesenteric arteries (225-450 μm inner diameter) were mounted in organ baths for recording isometric tension. In arteries precontracted with U46619 (thromboxane A2 analogue, 10^-7 M), endothelium-dependent relaxations were induced in a concentration-dependent manner by substance P and histamine. In normal Krebs solution the relaxations to substance P (10^-9 M) and histamine (10^-7 M) were not significantly affected by preincubation with Nω-nitro-L-arginine (L-NNA, 10^-4 M) or indomethacin (10^-5 M). When the preparations were exposed to a solution containing 60 mM KCl, stable contractions were induced, but relaxations could still be induced by substance P and histamine. When the arteries were further preincubated with L-NNA, the relaxations were almost abolished. A combination of apamin (3 x 10^-7 M) and charybdotoxin (10^-9 M) almost abolished relaxations in normal Krebs solution. It is concluded that isolated human mesenteric arteries respond to substance P and histamine with relaxations that are endothelium-dependent. Synthesis of both EDNO and EDHF seem important for these relaxations, whereas prostaglandins seem to be of minor importance.


Key words
Human artery • Nitric oxide • EDHF • Potassium channels • High potassium solution