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tPA contributes to impairment of ATP and Ca sensitive K channel mediated cerebrovasodilation after hypoxia/ischemia through upregulation of ERK MAPK
| Content Provider | Semantic Scholar |
|---|---|
| Author | Armstead, William M. Riley, John G. Cines, Douglas B. Higazi, Abd Al-Roof |
| Copyright Year | 2011 |
| Abstract | The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, tPA potentiates impairment of pial artery dilation in response to hypotension after hypoxia/ischemia (H/I) in pigs. ATP and Ca sensitive K channels (Katp and Kca) are important regulators of cerebrovascular tone and mediate cerebrovasodilation in response to hypotension. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is upregulated after H/I, with the ERK isoform contributing to vasodilator impairment. This study examined the effect of H/I on Katp and Kca induced pial artery dilation and the roles of tPA and ERK during/after injury in piglets equipped with a closed cranial window. H/I blunted vasodilation induced by the Katp agonists cromakalim, calcitonin gene related peptide (CGRP) and the Kca agonist NS 1619; the effect of each was exacerbated by tPA. Pre- or post-injury treatment with EEIIMD, a hexapeptide derived from plasminogen activator-1, and ERK antagonist U 0126 prevented Katp and Kca channel agonist induced vasodilator impairment while the inactive analogue EEIIMR had no effect. ERK was upregulated after H/I, which was potentiated by tPA. These data indicate that H/I impairs K channel mediated cerebrovasodilation. tPA augments loss of K channel function after injury by upregulating ERK. These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by impairing cation-mediated control of cerebrovascular tone. |
| Starting Page | 88 |
| Ending Page | 93 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.brainres.2010.12.052 |
| PubMed reference number | 21182829 |
| Journal | Medline |
| Volume Number | 1376 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0006899310027393 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0006899310027393?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.brainres.2010.12.052 |
| Journal | Brain Research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
