TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and blood pressure in 1‐2‐week old but not adult rats

Shvetsova, A.A.; Gaynullina, D.K.; Schmidt, N.; Bugert, P.; Lukoshkova, E.V.; Tarasova, O.S.; Schubert, R.

Авторы: Shvetsova Anastasia A., Gaynullina Dina K., Schmidt Nadine, Bugert Peter, Lukoshkova Elena V., Tarasova Olga S., Schubert Rudolf
Журнал: British Journal of Pharmacology
Том: 177
Номер: 22
Год издания: 2020
Издательство: Nature Publishing Group
Местоположение издательства: United Kingdom
Первая страница: 5148
Последняя страница: 5162
Номер статьи: bph.15249
DOI: 10.1111/bph.15249
Аннотация: Background and Purpose: The vasomotor role of K2P potassium channels during early postnatal development has never been investigated. We tested the hypothesis that TASK-1 channel (K2P family member) contribution to arterial vascular tone and blood pressure is higher in the early postnatal period than in adulthood. Experimental Approach: We studied 10- to 15-day-old («young») and 2- to 3-month-old («adult») male rats performing dPCR (using endothelium-intact saphenous arteries), isometric myography, sharp microelectrode technique, qPCR and Western blotting (using endothelium-denuded saphenous arteries) and arterial pressure measurements under urethane anesthesia.Key Results: We found mRNA of Kcnk1- Kcnk7, Kcnk12 and Kcnk13 genes to be expressed in rat saphenous artery, Kcnk3 (TASK-1) and Kcnk6 (TWIK-2) were most abundant in both age groups. The TASK-1 channel blocker AVE1231 (1 μmol L-1) prominently depolarized arterial smooth muscle and increased basal tone level and contractile responses to methoxamine of arteries from young rats, but had almost no effect in adult rats. The level of TASK-1 mRNA and protein expression were higher in arteries from young compared to adult rats. Importantly, intravenous administration of AVE1231 (4 mg kg-1) had no effect on mean arterial pressure in adult rats but prominently raised it in young rats.Conclusion and Implications: We showed that TASK-1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. The influence of TASK-1 channels most likely contributes to low blood pressure level at perinatal age.
Добавил в систему: Швецова Анастасия Алексеевна

	ИСТИНА	Войти в систему Регистрация
	Интеллектуальная Система Тематического Исследования НАукометрических данных
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

Интеллектуальная Система Тематического Исследования НАукометрических данных

TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and blood pressure in 1‐2‐week old but not adult ratsстатья

Прикрепленные файлы