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Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated $K^{+}$ $(K_{V}$) Channels
| Content Provider | MDPI |
|---|---|
| Author | Hasan, Ahasanul Hasan, Raquibul |
| Copyright Year | 2021 |
| Description | 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 $K_{V}$1.5 and $K_{V}$7 abolished empagliflozin-induced vasodilation. In contrast, pharmacological inhibition of large-conductance $Ca^{2+}$-activated $K^{+}$ $(BK_{Ca}$) channels and ATP-sensitive $(K_{ATP}$) 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 $(PGI_{2}$) 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 $K_{V}$ channels $K_{V}$1.5 and $K_{V}$7, 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. |
| Starting Page | 10842 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms221910842 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 19 |
| Volume Number | 22 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-10-07 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Peripheral Vascular Disease Empagliflozin Mesenteric Arteries Smooth Muscle Cell Voltage-gated K+ Channels Vasodilation |
| Content Type | Text |
| Resource Type | Article |
