Role of BKCa Channels in Pial-Vessel Dilation in Rats of Different Ages

Abstract

Studying the mechanisms of age-related changes in vascular reactions and applying the acquired knowledge in clinics can help reduce complications and mortality from diseases of the cardiovascular system, the frequency of which increases with age. This study is important because with aging, endothelial dysfunction increases and cerebral circulation disorders caused by the occurrence of ischemic foci are observed. One of the main elements in the regulation of vascular tone, along with many important mechanisms, is potassium ion channels. In this work, we study age-related changes in the role of calcium-activated potassium channels (BK_Ca) in the acetylcholine-mediated dilation of cerebral arteries in Wistar rats, since their contribution to vasodilation in aging is poorly understood. Using intravital microphotography (×470), we compare the responses of pial arteries to acetylcholine chloride (ACh, 10^–7 M, 5 min) in the absence and against the background of BK_Ca blockade with tetraethylammonium chloride (TEA, 2 mM, 5 min) in Wistar rats 4, 6, 9, 18 and 24 months old. Changes in the contribution of BK_Ca to vascular dilation are assessed by changes in the number of dilations of the pial arteries upon exposure to ACh after BK_Ca blockade, measuring the width of vessels in 3 separate groups of arteries: small (with a diameter of less than 20 μm), medium (20–40 μm), and large (more than 40 μm). It has been shown that ACh-induced dilation depends on the initial diameter of the arteries. The inhibition of BK_Ca activity in 4-month-old rats reduces the number of ACh-induced dilations in all groups of arteries studied. Compared to 4-month-old rats, in 6- and 18-month-old rats the contribution of BK_Ca channels to the dilation of small arteries is reduced, in 9- and 24-month-old rats the contribution of BK_Ca channels to the dilation of medium arteries is increased; the contribution of BK_Ca to the dilation of large arteries decreases starting from 6 months of age. Dilation of the pial arteries of Wistar rats at the age of 4–24 months depends on the initial diameter of the vessel. BK_Ca play a significant role in the ACh-mediated dilation of these vessels. Age-related impairments in the contribution of these channels to the ACh-mediated dilation of pial arteries develop gradually, have a wave-like course and depend on the diameter of the arteries. The identified disturbances in the functional activity of BK_Ca can serve as therapeutic targets for the creation of new technologies for the treatment of age-related lesions of cerebral vessels.