Ali PARLAR, Saliha Ayşenur ÇAM, Ahmet Cenk ANDAÇ, Ibraheem Akram OMAR, Fatma UYSAL, Seyfullah Oktay ARSLAN, Muhammed Fatih DOĞAN, Oğuzhan YILDIZ

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

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 $(Ca^{2+})$ ion channel blocker, nilvadipine (10 μM); 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 $Ca^{2+}$ channels was examined using $Ca^{2+}$-free Krebs solution, and adding calcium chloride $(CaCl_2, 10^{-5}– 10^{-2} M)$ 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 $CaCl_2$, PE, or KCl on HCQ-incubated RA rings (p < 0.05). The incubation of the RA rings with the $Ca^{2+}$ 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 $Ca^{2+}$ channel inhibition is involved at concentrations of 10-5 and 10-4 M, as well as NO.

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