Modulation of Vascular Reactivity by Novel Synthetic Benzopyran Analogues in Rat Aortas

Abstract

A substantial body of research described ATP-dependent potassium (K ATP ) channels, sarcolemmal and mitochondrial, with different physiological functions and pharmacological behaviour in various tissues (pancreatic â-cells, brain, skeletal muscle and vascular smooth muscle). The present study was purported to assess the effects of three novel benzopyran derivatives, KL-1487, KL-1492 and KL-1507, analogues of BMS191095 (a selective opener of mitoK ATP channels) on vascular function and reactive oxygen species (ROS) production. To this aim, we performed organ bath experiments on rat aortic rings in the presence vs. absence of each of the mentioned compounds (10 µmol/L). Incubation of vascular rings with each benzopyran analogue elicited a significant decrease of the contractile response to phenylephrine vs. control, thus suggesting a vasodilator action. However, only two of the benzopyran derivatives, KL-1492 and KL-1507, significantly improved the endothelial-dependent relaxation. Interestingly, these effects were present also in endothelium denuded vessels. None of these compounds modified vascular ROS production. In conclusion, in murine aortic segments, KL-1492 and KL-1507, two novel benzopyran analogues elicited an endothelial- independent modulation of vascular reactivity. Further studies will elucidate whether these compounds may be useful in restoring the vascular response in pathological conditions associated with endothelial dysfunction. Keywords: benzopyran derivatives, endothelial function, organ bath, vascular murine ring