Potassium-channel openers KMUP-1 and pinacidil prevent subarachnoid hemorrhage-induced vasospasm by restoring the BKCa-channel activity

Shock
Jun-Yih ChenBin-Nan Wu

Abstract

Alterations in the activity of vascular K channels are commonly associated with abnormalities in cerebral vascular function after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage-induced vasospasm remains incompletely understood; nevertheless, activation of K channels may be of benefit in relieving spastic constriction. This study was to examine whether the vasodilators KMUP-1 and pinacidil, a KATP-channel opener, have the ability to prevent SAH-induced vasospasm via the large-conductance Ca-activated K (BKCa) channels in cerebral arteries. Rats were divided into four groups including sham-operated, SAH, KMUP-1 treated, and pinacidil treated. Subarachnoid hemorrhage rats were induced by injecting autologous blood into cisterna magna, and then KMUP-1 or pinacidil (1 mg/kg) was injected intraperitoneally 1 and 24 h after SAH. Behavioral tests were assessed on day 2 after SAH before the rats were killed. Cerebral myocytes were enzymatically isolated from rat basilar arteries and used to monitor BKCa-channel activities. In isolated basilar arteries, KMUP-1-treated and pinacidil-treated rats showed normalized vascular reactivity. In whole-cell recordings, BKCa currents were attenuated in SAH rats compared with sham-operated ra...Continue Reading

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Citations

May 23, 2013·International Journal of Urology : Official Journal of the Japanese Urological Association·Chi-Ming LiuIng-Jun Chen
Mar 8, 2013·Immunopharmacology and Immunotoxicology·Kwang Sik SuhEun Mi Choi
Oct 22, 2014·Molecular Medicine Reports·Eun Mi ChoiKwang Sik Suh

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