Interleukin-2 causes endothelium-dependent contractions to arachidonic acid.

Abstract

The present experiments were designed to investigate the effect of interleukin-2 on the response to arachidonic acid in rings with and without endothelium from Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) aortas. In control rings, arachidonic acid induced contractions of WKY aorta that were not different between preparations with and without endothelium. Incubation with interleukin-2 (10 units/mL) for 6 or 18 hours augmented the response to arachidonic acid in rings with, but not in those without, endothelium from WKY rat aortas. In the WKY aorta, both the endothelium-dependent and endothelium-independent contractions to arachidonic acid observed after incubation with interleukin-2 were abolished by indomethacin and ridogrel (a thromboxane-endoperoxide receptor antagonist and a thromboxane synthase inhibitor) but were not affected by dazoxiben (a thromboxane synthase inhibitor). Interleukin-2 did not augment the vascular reactivity of WKY aortic smooth muscle to activation of the thromboxane-endoperoxide receptor with U46619. In aortas from SHRs, arachidonic acid evoked endothelium-dependent contraction; interleukin-2 did not modify the response to arachidonic acid in preparations with and without endothelium. These data demonstrate that 1) endothelium-dependent contractions to arachidonic acid are observed in SHR but not in WKY rat aortas; 2) interleukin-2 induces endothelium-dependent contractions to arachidonic acid in the WKY aorta that are mediated by an augmented release of a metabolite of cyclooxygenase, different from thromboxane A2 but activating thromboxane-endoperoxide receptors; and 3) interleukin-2 does not affect the endothelium-dependent and endothelium-independent response to arachidonic acid in the SHR aorta.