PTK, MAPK, and NOC/oFQ impair hypercapnic cerebrovasodilation after hypoxia/ischemia.
This study characterized the contributions of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in nociceptin/orphanin FQ (NOC/oFQ)-induced impairment of hypercapnic pial artery dilation (PAD) after hypoxia/ischemia (H/I) in piglets equipped with a closed cranial window. NOC/oFQ (10(-10) M cerebrospinal fluid H/I concentration) impaired hypercapnic PAD (21 +/- 2% vs. 13 +/- 1%). Coadministration of either of the PTK inhibitors genistein or tyrphostin A23 or the MAPK inhibitors U-0126 or PD-98059 with NOC/oFQ (10(-10) M) partially prevented the inhibition of hypercapnic PAD compared with that observed in their absence (21 +/- 2% vs. 17 +/- 1% for genistein). After exposure to H/I, PAD in response to hypercapnia was impaired, but pretreatment with either genistein, tyrphostin A23, U-0126, or PD-98059 partially protected such impairment (17 +/- 1% vs. 4 +/- 1% vs. 9 +/- 1% for sham control, H/I, and H/I + genistein pretreatment, respectively). These data show that PTK and MAPK activation contribute to NOC/oFQ-induced impairment of hypercapnic PAD. These data suggest that activation of PTK and MAPK is also involved in the mechanism by which NOC/oFQ impairs hypercapnic PAD after H/I.
Jagolino
Amanda L
AL
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
Armstead
William M
WM
D000818:Animals; D001158:Arteries / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D018847:Opioid Peptides / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013552:Swine; D014664:Vasodilation; D000097629:Nociceptin
D020928:Mitogen-Activated Protein Kinases; D018847:Opioid Peptides; D011505:Protein-Tyrosine Kinases; D000097629:Nociceptin