Opioids and nitric oxide contribute to hypoxia-induced pial arterial vasodilation in newborn pigs.
The present study was designed to investigate the contribution of opioids and nitric oxide (NO) to hypoxia-induced pial vasodilation. Newborn pigs equipped with a closed cranial window were used to measure pial arteriolar diameter and to collect cortical periarachnoid cerebrospinal fluid (CSF) for assay of opioids and guanosine 3',5'-cyclic monophosphate (cGMP). Hypoxia-induced pial dilation was potentiated by norbinaltorphimine, 10(-6) M, a kappa-opioid antagonist (25 +/- 2 vs. 33 +/- 3%, n = 5), but was blunted by beta-funaltrexamine, 10(-8) M, a mu-opioid antagonist (28 +/- 2 vs. 19 +/- 1%, n = 5). Hypoxia-induced vasodilation was associated with increased CSF methionine enkephalin, a mu-opioid agonist (884 +/- 29 vs. 2,638 +/- 387 pg/ml, n = 5). N omega-nitro-L-arginine (L-NNA), an NO synthase inhibitor (10(-6) M), also blunted hypoxia-induced vasodilation that was further diminished by coadministration of L-NNA and beta-funaltrexamine (26 +/- 2, 14 +/- 1, and 9 +/- 1%, respectively, n = 5). Reversal of the above order of antagonist administration resulted in similar inhibition of hypoxia-induced pial dilation. Hypoxia-induced vasodilation was also associated with an increase in CSF cGMP that was attenuated by L-NNA (2.1 +/- 0.1- vs. 1.1 +/- 0.2-fold change in CSF cGMP, n = 5). Sodium nitroprusside (10(-6) M) increased CSF cGMP and methionine enkephalin concentration similar to hypoxia. These data suggest that hypoxia-induced pial arterial vasodilation, in part, is due to NO and/or cGMP-induced methionine enkephalin release as well as the direct action of NO.
Armstead
W M
WM
Department of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia.
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006152:Cyclic GMP / Q000134:cerebrospinal fluid; D004399:Dynorphins / Q000134:cerebrospinal fluid*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000134:cerebrospinal fluid*; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004745:Enkephalins; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; C051844:norbinaltorphimine; D004744:Enkephalin, Methionine; D009271:Naltrexone; C024524:beta-funaltrexamine; D004399:Dynorphins; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP