PRO-HYPERTENSIVE ENDOTHELIAL DYSFUNCTION DUE TO LOWER EXTRACELLULAR MAGNESIUM INVOLVES IK1 CHANNELS

Endothelium-dependent relaxation (EDR) in resistance arteries is largely independent of nitric oxide (NO) synthase and cyclooxygenase. It is mediated by endothelium-dependent hyperpolarization (EDH), based on endothelial Ca2+-activated K+ channels: IK1 with intermediate conductance (iK) and SK3 with small conductance (sK). Mg2+ modulates vascular reactivity directly and via NO-mediated EDR. Aim: We examined effects of diminished extracellular Mg2+ (Mge) concentration upon EDH-mediated EDR. Material and methods: Using wire myography, we tested isolated small mesenteric arteries from male rat. EDH-mediated EDR was induced by acetylcholine 10-8-10-4 M, in vascular rings contracted by phenylephrine 10-5 M, in presence of l-NAME 10-4 M and indomethacin 10-5 M, with [Mge] kept at 1.2 mM (regular) or 0.8 mM (lower). Results: EDH-mediated EDR was inhibited by lower [Mge] (n=6; p<0.001; multiple t-test). Maximal EDH-mediated EDR was reduced from 75.79±2.6 % in regular [Mge] to 64.64±2.53 % in lower [Mge]. iK blocker TRAM-34 inhibited EDH-mediated EDR similarly in regular and lower [Mge], but sK blocker UCL 1684 inhibited EDH-mediated EDR more in lower [Mge] than in regular [Mge] (n=6; p<0.001; multiple t-test). Thus, lower [Mge] inhibits EDH-mediated EDR further when sK are blocked, but not when iK are blocked. Conclusions: Lower [Mge] inhibits EDH-mediated EDR, due to negative interference with iK. This novel pro-hypertensive mechanism is relevant for endothelial dysfunction in arterial hypertension associated with hypomagnesemia and for Mg therapy in general.