Endothelium-Independent Vasorelaxant Effect of Synthesized 2 Hydroxymethylchromone on Rat Mesenteric Arterial Bed

Background: Several synthesized chromones derivatives have been found to promote intense vasodilation and antihypertensive activity. 2 hydroxymethylchromone (2HMC) is a benzopyrane derivative that vasodilator effect on small arteries has not yet been investigated. This study describes its synthesis, examines any vasodilator effect observed, and clarifies its mechanism of action in rat mesenteric arterial bed (MAB). Material and Method: Intact and denuded rat mesenteric arterial bed pre-contracted with PHE (2-4 ng/mL) was exposed to bolus injections of 2HMC (3-1000 μg). The effect of the latter was also studied in the presence of specific inhibitors such as L-NAME, indomethacine, atropine, glybenclamide, tetraethylammonium, BaCl2 and apamin. The effect of 2HMC on restricted calcium influx and calcium release from sarcoplasmic reticulum was investigated. Results: The data show that bolus injections of 2HMC induced in a dose dependent manner, a reversible vasorelaxant effect on pre-contracted preparations. This effect remained unaltered by endothelium removal and was not significantly affected by L-NAME, indomethacine, atropine, glybenclamide, BaCl2 tetraethylammonium or apamin. On the contrary, 2HMC significantly shifted to the right the concentration-response curve to high K+-induced MAB contraction during Ca2+ supplementation. Also, 2HMC strongly reduced the response to PHE when the MAB(s) were maintained under calcium-free conditions. Conclusion: Our results suggest that 2HMC-induced vasorelaxation is not mediated via the endothelium pathways, but rather might be due at least to both antagonistic action on extracellular calcium influx (blockade of voltage operated calcium channels) and restriction of calcium mobilization from intracellular stores.