The role of nitric oxide in opioid-induced pial artery vasodilation.
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)
Devine
J O
JO
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
Armstead
W M
WM
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*
D009294:Narcotics; D011957:Receptors, Opioid; D009569:Nitric Oxide; D006152:Cyclic GMP