Hydroxychloroquine induces endothelium-dependent and endothelium-independent relaxation of rat aorta

Authors: SEYFULLAH OKTAY ARSLAN, MUHAMMED FATİH DOĞAN, SALİHA AYŞENUR ÇAM, IBRAHEEM AKRAM OMAR, FATMA UYSAL, ALİ PARLAR, AHMET CENK ANDAÇ, OĞUZHAN YILDIZ

Abstract: Background/aim: Hydroxychloroquine (HCQ) is an antimalarial that is widely used in the management of rheumatoid arthritis and other autoimmune diseases. In this study, we aimed to examine the vascular effects of HCQ on rat aorta (RA). Materials and methods: The RA rings were suspended in isolated organ baths and tension was recorded isometrically. HCQ-induced relaxations were tested in the presence of the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (L-NAME, 100 mM); the cyclooxygenase enzyme inhibitor, indomethacin (10 mM); the calcium (Ca2+) ion channel blocker, nilvadipine (10 ?M); and the K+ ion channel inhibitors, tetraethylammonium (1 mM), glibenclamide (10 mM), 4-aminopyridine (1 mM), and barium chloride (30 mM). The effect of HCQ on Ca2+ channels was examined using Ca2+-free Krebs solution, and adding calcium chloride (CaCl2, 10-5? 10-2 M) cumulatively to baths incubated with HCQ. Results: Removing the endothelium resulted in less relaxation of RA rings compared to endothelium-intact rings (p < 0.05). The effect of endothelium was supported by using L-NAME where HCQ produced-vasorelaxation was decreased (p < 0.05). The contraction of vascular rings was inhibited to a significant degree following the addition of CaCl2, PE, or KCl on HCQ-incubated RA rings (p < 0.05). The incubation of the RA rings with the Ca2+ channel blocker, the K+ channel blockers, and the COX inhibitor, indomethacin did not significantly affect vascular relaxation induced by HCQ. Conclusion: HCQ produced relaxation of RA rings. The relaxation mechanism differs according to the concentration of HCQ. At concentrations of 10-6 and 10-5 M, the relaxation is endothelium-dependent and mediated by NO. We strongly suggest that Ca2+ channel inhibition is involved at concentrations of 10-5 and 10-4 M, as well as NO.

Keywords: Hydroxychloroquine, nitric oxide, calcium channels, vasodilation

Full Text: PDF