PTK, MAPK, and NOC/oFQ impair hypercapnic cerebrovasodilation after hypoxia/ischemia.

Abstract

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.

• Authors: Amanda L Jagolino, William M Armstead
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 284 Issue 1 Pg. H101-7 (Jan 2003) ISSN: 0363-6135 [Print] United States
• PMID: 12485817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Opioid Peptides
• nociceptin
• Protein-Tyrosine Kinases
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Arteries (physiopathology)
• Cerebrovascular Circulation
• Female
• Hypercapnia (physiopathology)
• Hypoxia (physiopathology)
• Ischemia (physiopathology)
• Male
• Mitogen-Activated Protein Kinases (physiology)
• Opioid Peptides (physiology)
• Pia Mater (blood supply)
• Protein-Tyrosine Kinases (physiology)
• Swine
• Vasodilation