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 the clinic 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, are potassium ion channels. In this work, we studied age-related changes in the role of calcium-activated potassium channels (BKCa) in acetylcholine-mediated dilatation of cerebral arteries in Wistar rats, since their contribution to vasodilation in aging is poorly understood. Using intravital microphotography (×470), we compared the responses of pial arteries to acetylcholine chloride (ACh, 10-7 M, 5 min) in the absence and against the background of BKCa blockade with tetraethylammonium chloride (TEA, 2 mM, 5 min) in aged Wistar rats 4, 6, 9, 18 and 24 months. Changes in the contribution of BKCa to vascular dilatation were assessed by changes in the number of dilatations of the pial arteries on the exposure to ACh after BKCa 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 dilatation depends on the initial diameter of the arteries. Inhibition of BKCa activity in 4-month-old rats reduces the number of ACh-induced dilatations in all groups of arteries studied. Compared to 4-month-old rats, in 6- and 18-month-old rats the contribution of BKCa channels to the dilatation of small arteries is reduced, in 9- and 24-month-old rats the contribution of BKCa channels to the dilatation of medium arteries is increased; the contribution of BKCa to the dilatation of large arteries decreases starting from 6 months of age. Dilatation of the pial arteries of Wistar rats at the age of 4–24 months depends on the initial diameter of the vessel. BKCa play a significant role in ACh-mediated dilatation of these vessels. Age-related impairments in the contribution of these channels to ACh-mediated dilatation 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 the BKCa can serve as therapeutic targets for the creation of new technologies for the treatment of age-related lesions of cerebral vessels.