ИСТИНА

Aim: Activation of K+-channels is a key mechanism of vascular smooth muscle hyperpolarization and relaxation. We tested the hypotheses that the role K+-channels play in the regulation of vasocontractile responses varies with postnatal maturation. Methods: Segments of saphenous artery were isolated from young (10-15-days old) and adult (2-3-month old) male rats and studied using wire myography. We used blockers of KATP (glibenclamide, 3 microM), Kv7 (XE991, 3 microM) and BKCa (iberiotoxin, 0.1 microM) channels to evaluate their influence on basal tone and contractile responses to the alpha1-adrenoceptor agonist methoxamine. mRNA contents were determined by qPCR. Results: Glibenclamide had no effect on basal tone and contractile responses of arteries in either young or adult rats. XE991 caused a significant increase of contractile responses and basal tone in young, but not adult rats; this was consistent with higher expression levels of Kv7.1 and Kv7.5 alpha-subunits in young rat arteries. Iberiotoxin augmented vasocontractile responses in both groups, in accordance with no between-group difference of BKCa (alpha-subunit) expression levels. Notably, endothelium denudation enhanced the effects of XE991 and iberiotoxin on arteries of young but not adult rats. Conclusions: We demonstrated that KATP channels have no impact on contractile responses to alpha1-adrenоceptor agonist in both age groups; the influence of BKCa channels is not dependent on age, while the contribution of Kv7 channels decreases with maturation. The endothelium modulates the activity of BKCa and Kv7 channels in arteries of young rats. Supported by RFBR (grant N14-04-31377) and RSF (grant N14-15-00704).