Возрастные изменения вклада NO и калиевых каналов в дилатацию пиальных артериальных сосудов у крыс

Abstract

Calcium-dependent high-conductance potassium channels (BKCa-channels) play an important role in signaling from NO produced by endothelium to vascular smooth muscle cells. The aim of this work was to study age-related changes in the contribution of NO and BKCa-channels to acetylcholine (ACh)-induced dilatation of pial arteries and to assess the role of eNOS- and iNOS-produced NO in Wistar rats at the age of 4 and 9 months. For this, the mechanisms of regulation of vascular tone were turned off using blockers, and the change in the diameter of the pial arteries to acetylcholine (ACh) against the background of blockade of BKCa-channels with tetraethylammonium (TEA), NO – L-NAME, iNOS – aminoguanidine (AG) was recorded by the method of intravital microphotography. The number of dilatations and the degree of dilatation of the pial arteries in response to ACh were determined. These data were compared with data obtained in the absence of blockade. The contribution of the mechanisms mediated by the activation of BKCa channels, eNOS and iNOS, to the dilatation of 3 groups of pial arteries: small (less than 20 µm in diameter), medium (20–40 µm), and large (more than 40 µm) was evaluated. In young rats, NO produced by eNOS makes a significant contribution to the regulation of AX-induced vasodilation of medium and large arteries, while in small arteries, activation of BKCa channels predominates. With age, the contribution of eNOS-mediated mechanisms to the dilatation of the middle and large arteries decreases, but iNOS is included in the dilatation process, and the contribution to the maintenance of the basal tone and functional activity of the BKCa channels of the middle and large pial arteries increases, which is dependent of NO produced iNOS.