title: The role of nitric oxide in opioid-induced pial artery vasodilation.
abstract: The present study was designed to investigate the role of nitric oxide (NO) and the production of cGMP in the vasodilator response to opioid agonists in newborn pigs equipped with a closed cranial window. Methionine-enkephalin (10(-8), 10(-6) M), an endogenous mu opioid agonist, produced pial artery dilation that was attenuated by L-nitroarginine (LNA, 10(-6) M), an NO synthase inhibitor (10 +/- 1 vs. 4 +/- 1 and 16 +/- 1 vs. 7 +/- 1% for 10(-8), 10(-6) M methionine-enkephalin, respectively). Methionine-enkephalin-induced vasodilation was associated with increased cortical periarachnoid CSF cGMP and these changes in CSF cGMP were attenuated by LNA (354 +/- 11 and 596 +/- 32 vs. 278 +/- 13 and 266 +/- 19 fmol/ml for control and methionine-enkephalin 10(-6) M before and after LNA, respectively). Leucine enkephalin, an endogenous delta agonist, elicited similar changes in pial diameter and CSF cGMP while dynorphin, an endogenous k agonist, produced dilation associated with large increases in CSF cGMP (374 +/- 18 vs. 1054 +/- 45 fmol/ml for control and dynorphin 10(-6) M, respectively). Vascular and biochemical changes for these two opioids were similarly attenuated by LNA. The synthetic selective opioid receptor agonists, DAMGO, DPDPE, deltorphin, and U50,488H (10(-8), 10(-6) M) mu, delta 1, delta 2, and kappa agonists, respectively, also elicited increases in pial artery diameter and CSF cGMP that were similarly attenuated by LNA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Devine
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply*; D011957:Receptors, Opioid / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009294:Narcotics; D011957:Receptors, Opioid; D009569:Nitric Oxide; D006152:Cyclic GMP