Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers
| Autor: | Lars S Kruse, Faisal Mohammad Amin, Samaira Younis, Anders Hougaard, Messoud Ashina, Mark B Vestergaard, Afrim Iljazi, Kazutaka Sugimoto, Cenk Ayata, Ulrich Lindberg, Kristian Agmund Haanes |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male endocrine system Middle Cerebral Artery Vasodilation Pharmacology Cerebral edema Glibenclamide 03 medical and health sciences 0302 clinical medicine medicine.artery medicine Humans Vasoconstrictor Agents cardiovascular diseases Infusions Intravenous 030304 developmental biology 0303 health sciences Endothelin-1 business.industry Brain Original Articles medicine.disease Magnetic Resonance Imaging Healthy Volunteers Cerebral Angiography Neurology Cerebral blood flow Vasoconstriction Cerebrovascular Circulation Middle cerebral artery cardiovascular system Sulfonylurea receptor Female Spin Labels Neurology (clinical) Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Endothelin receptor business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | J Cereb Blood Flow Metab |
| ISSN: | 1559-7016 |
| Popis: | Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (KATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits KATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated.In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and KATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of KATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of KATP channel activation during hypoxia and ischemia-induced brain injury. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|