Metformin relaxes rat thoracic aorta via nitric oxide, AMPK, potassium channels, and PKC

Objective(s): The present research aimed to identify the functional effects and underlying mechanisms of metformin on the rat thoracic aorta.Materials and Methods: Thoracic aorta segments of Wistar Albino rats were put in the chambers of an isolated tissue bath system. The resting tone was adjusted to ۱ g. Following the equilibration time, potassium chloride or phenylephrine was used to contract the vascular segments. The vessel segments were cumulatively treated with metformin (۱۰-۷–۱۰-۳ M) when a steady contraction was achieved. The described experimental approach was repeated after incubations with signaling pathway inhibitors and selective blockers of potassium channels to identify the effect mechanisms of metformin.Results: Metformin had a potent vasorelaxant effect in a concentration-dependent way (P<۰.۰۰۱). After the endothelium was removed, the vasorelaxant effect level of metformin was significantly reduced. The level of vasorelaxant effect of metformin was increased by the maintenance of perivascular adipose tissue. Following administrations of L-NAME, methylene blue, compound C, BIM-I, and potassium channel blockers, the level of vasodilatory action of metformin was significantly reduced (P<۰.۰۰۱).Conclusion: According to the results of this investigation, metformin significantly relaxes the thoracic aorta segments of rats. Metformin-mediated vasorelaxation involves the activation of numerous subtypes of potassium channels, including BKCa, IKCa, Kv, Kir, and K۲p channels, as well as endothelium-dependent processes, including AMPK and eNOS/NO/sGS signaling pathways. Moreover, metformin-induced vasorelaxation is mediated through PVAT activation and the PKC signaling pathway.

Keywords:

Metformin , Nitric oxide , Potassium channels , Rat , thoracic aorta