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Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels

Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA
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Author to whom correspondence should be addressed.
Academic Editor: Sabata Pierno
Int. J. Mol. Sci. 2021, 22(19), 10842; https://doi.org/10.3390/ijms221910842
Received: 16 August 2021 / Revised: 26 September 2021 / Accepted: 4 October 2021 / Published: 7 October 2021
(This article belongs to the Section Molecular Pharmacology)
The antidiabetic drug empagliflozin is reported to produce a range of cardiovascular effects, including a reduction in systemic blood pressure. However, whether empagliflozin directly modulates the contractility of resistance-size mesenteric arteries remains unclear. Here, we sought to investigate if empagliflozin could relax resistance-size rat mesenteric arteries and the associated underlying molecular mechanisms. We found that acute empagliflozin application produces a concentration-dependent vasodilation in myogenic, depolarized and phenylephrine (PE)-preconstricted mesenteric arteries. Selective inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 and KV7 abolished empagliflozin-induced vasodilation. In contrast, pharmacological inhibition of large-conductance Ca2+-activated K+ (BKCa) channels and ATP-sensitive (KATP) channels did not abolish vasodilation. Inhibition of the vasodilatory signaling axis involving endothelial nitric oxide (NO), smooth muscle cell soluble guanylyl cyclase (sGC) and protein kinase G (PKG) did not abolish empagliflozin-evoked vasodilation. Inhibition of the endothelium-derived vasodilatory molecule prostacyclin (PGI2) had no effect on the vasodilation. Consistently, empagliflozin-evoked vasodilation remained unaltered by endothelium denudation. Overall, our data suggest that empagliflozin stimulates smooth muscle cell KV channels KV1.5 and KV7, resulting in vasodilation in resistance-size mesenteric arteries. This study demonstrates for the first time a novel mechanism whereby empagliflozin regulates arterial contractility, resulting in vasodilation. Due to known antihypertensive properties, treatment with empagliflozin may complement conventional antihypertensive therapy. View Full-Text
Keywords: empagliflozin; mesenteric arteries; smooth muscle cell; voltage-gated K+ channels; vasodilation empagliflozin; mesenteric arteries; smooth muscle cell; voltage-gated K+ channels; vasodilation
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MDPI and ACS Style

Hasan, A.; Hasan, R. Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels. Int. J. Mol. Sci. 2021, 22, 10842. https://doi.org/10.3390/ijms221910842

AMA Style

Hasan A, Hasan R. Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels. International Journal of Molecular Sciences. 2021; 22(19):10842. https://doi.org/10.3390/ijms221910842

Chicago/Turabian Style

Hasan, Ahasanul, and Raquibul Hasan. 2021. "Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels" International Journal of Molecular Sciences 22, no. 19: 10842. https://doi.org/10.3390/ijms221910842

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