Age-Related Changes in the Role of Calcium-Activated Potassium Channels in Acetylcholine Mediated Dilatation of Pial Arterial Vessels in Rats

Abstract

Age-related changes in the contribution of endothelial hyperpolarization evoked by activation of intermediate-conductance Ca2+-activated K+ (IKca) channels and NO to acetylcholine-mediated dilatation of pial arterial vessels in rats were studied. Using intravital microphotography (×470), a comparative evaluation of pial arterial responses to acetylcholine chloride (ACh, 10–7 M, 5 min) with and without blockade of IKCa channels (clotrimazole, 10–5 M) and NO (L-NAME, 10–3 M) was carried out in Wistar rats aged 4 and 26 months. The contribution of endothelial hyperpolarization and NO to vascular dilatation was evaluated by changes in the number of dilated arteries and the degree of their response to ACh after application of the blockers. For the latter purpose, the erythrocyte flow width was measured in three individual groups of arteries: small- (< 20 µm), medium- (20–40 µm) and large- (> 40 µm) caliber. The obtained data indicate an age-related decrease in the contribution of endothelial hyperpolarization evoked by activation of IKca channels to ACh-induced dilatation of small-caliber pial arteries in rats. At the same time, the role of this mechanism in medium-caliber arteries increases. Apparently, changes in the vasodilatation mechanisms that occur during aging are due to an increasing role of NO-mediated regulation of endothelium-dependent dilatation responses.