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Hypotensive effect of oxatriazolium-5-olate derivative in spontaneous hypertensive rats (SHR) during chronic introductionстатья
Дата последнего поиска статьи во внешних источниках: 28 мая 2015 г.
- Авторы: Artemieva M.M., Akinfieva O.V., Postnikov A.B., Daliger I.L., Shevelev S.A., Medvedev O.S., Medvedeva N.A.
- Журнал: Acta physiologica Scandinavica
- Том: 193
- Номер: 664
- Год издания: 2008
- Издательство: Blackwell Scientific Publications
- Местоположение издательства: Oxford, England
- Первая страница: 103
- Последняя страница: 103
- Аннотация: Soluble guanylate cyclase (sGC) is a crucial enzyme at NO/cGMP-mediated vasodilation. There are NO-independent mechanisms of sGC activation besides wellknown enzyme activation by NO. Since 1966 oxatriazolium-5-olate derivatives are known as hypotensive agents at narcotized animals (Kier LB et al., 1966). But the mechanism of their activity is not clarified. To examine hypotensive activity of novel oxatriazolium-5-olate derivative AS-6 it was administrated per os during 3 weeks in dose 5 mg/kg twice a day to male SHR rats (200-300 g weight). Control group was administrated with appropriate water solutions. Systolic pressure was measured every 5 days by tail cuff. To examine mechanism of hypotensive effect of AS-6 it was used preparation of isolated caudal artery. It were perfused by AS-6 (6*10-5 М) and sodium nitroprusside solutions (1×10-6 М) in phenylephrine (5*10-6 М) and phenylephrine (5*10-6 М)+1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (3*10-6 М) tonus. Oral administration of AS-6 in dose 5 mg/kg twice a day during 21 days leads to systolic MAP decrease in SHR (10,5±2,5% in experiment, 4,1±.1,9% in control). Both AS-6 and SNP produced decrease of perfusion pressure (p<0,05) in caudal artery of experimental (63,2±4,0 % and 71,9±5,0% respectively) and control (60,7±5,5% and 68,8±6,4%, respectively) animals. ODQ significantly decreases vasodilatation caused by AS-6 and SNP both in experimental (8,4±2,3% and 15,2±2,8%, respectively) and control (13,9±6,6% and 30,5±8,6%, respectively) animals. So AS-6, as SNP, relaxes smooth muscle cells through activation of NO/sGC/cGMP-dependent mechanism. In vivo experiments showed that AS-6 has prolonged (14 days) hypotensive effect in SHR awake rats.
- Добавил в систему: Артемьева Марина Михайловна