Your browser doesn't support javascript.
loading
SKA-31, an activator of endothelial Ca2+-activated K+ channels evokes robust vasodilation in rat mesenteric arteries.
Khaddaj-Mallat, Rayan; Mathew John, Cini; Braun, Andrew P.
Afiliación
  • Khaddaj-Mallat R; Dept. of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
  • Mathew John C; Dept. of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
  • Braun AP; Dept. of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1. Electronic address: abraun@ucalgary.ca.
Eur J Pharmacol ; 831: 60-67, 2018 Jul 15.
Article en En | MEDLINE | ID: mdl-29753043
It is now well recognized that endothelial KCa2.3 and KCa3.1 channel activities contribute to dilation of resistance arteries via endothelium-mediated hyperpolarization and vascular smooth muscle relaxation. In this study, we have investigated the functional effect of the KCa channel activator SKA-31 in third order rat mesenteric arteries using arterial pressure myography. Isolated arteries were cannulated, pressurized intraluminally to 70 mmHg at 36 °C and then constricted with 1 µM phenylephrine. Acute bath exposure to SKA-31 evoked a robust and reversible inhibition of developed tone (IC50 = 0.22 µM). The vasodilatory effects of SKA-31 and acetylcholine were blunted in the presence of KCa2.3 and KCa3.1 channel antagonists, and were largely prevented following endothelial denudation. Western blot and q-PCR analyses of isolated mesenteric arteries revealed KCa2.3 and KCa3.1 channel expression at the protein and mRNA levels, respectively. Penitrem-A, an inhibitor of KCa1.1 channels, decreased vasodilatory responses to acetylcholine, sodium nitroprusside and NS-1619, but had little effect on SKA-31. Similarly, bath exposure to the eNOS inhibitor L-NAME did not alter SKA-31 and acetylcholine-mediated vasodilation. Collectively, these data highlight the major cellular mechanisms by which the endothelial KCa channel activator SKA-31 inhibits agonist-evoked vasoconstriction in rat small mesenteric arteries.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Vasodilatadores / Benzotiazoles / Canales de Potasio de Conductancia Intermedia Activados por el Calcio / Canales de Potasio de Pequeña Conductancia Activados por el Calcio / Arterias Mesentéricas Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2018 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Vasodilatadores / Benzotiazoles / Canales de Potasio de Conductancia Intermedia Activados por el Calcio / Canales de Potasio de Pequeña Conductancia Activados por el Calcio / Arterias Mesentéricas Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2018 Tipo del documento: Article Pais de publicación: Países Bajos