NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive cerebrovasodilation impairment.
Previous studies have observed that hypotensive pial artery dilation was blunted after hypoxia-ischemia. In unrelated studies, the opioid nociceptin/orphanin FQ (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D-aspartate (NMDA)-induced pial dilation. This study determined the contribution of NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment in newborn pigs equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased PO(2) to 33 +/- 3 mm Hg. Topical NOC/oFQ (10(-10) M), the cerebrospinal fluid concentration after hypoxia-ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) -induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial artery dilation was blunted by hypoxia-ischemia, but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M; 29 +/- 2%, sham control; 7 +/- 2%, hypoxia-ischemia; and 13 +/- 2%, hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH(2)). Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10(-10) M) partially prevented hypotensive pial dilation impairment. Similarly, pretreatment with MK801 partially protected hypoxic ischemia impairment of hypotensive pial dilation (35 +/- 2%, sham control; 7 +/- 1%, hypoxia-ischemia; 22 +/- 2%, hypoxia-ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic ischemic hypotensive cerebrovasodilation impairment. These data suggest that NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive impairment.
Armstead
William M
WM
Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. armsteaw@mail.med.upenn.edu
D000818:Animals; D000831:Animals, Newborn; D002560:Cerebrovascular Circulation / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007022:Hypotension / Q000150:complications / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D019586:Intracranial Hypertension / Q000150:complications; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D009292:Narcotic Antagonists; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D011957:Receptors, Opioid; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D018847:Opioid Peptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C439964:nociceptin (1-13) amide