The role of nitric oxide in opioid-induced pial artery vasodilation

• Published in: Brain research 1995-03, Vol.675 (1), p.257-263
• Main Authors: Devine, Joseph O., Armstead, William M.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn - physiology; Arteries - drug effects; Arteries - physiology; Biological and medical sciences; Blood Chemical Analysis; Blood Pressure - drug effects; Cerebral circulation; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; cGMP; Cyclic GMP - cerebrospinal fluid; Cyclic GMP - metabolism; Female; Fundamental and applied biological sciences. Psychology; Male; Narcotics - pharmacology; Newborn; Nitric Oxide - physiology; Pia Mater - blood supply; Receptors, Opioid - drug effects; Swine; Vasodilation - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00081-Z

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 μ 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 δ agonist, elicited similar changes in pial diameter and CSF cGMP while dynorphin, an endogenus 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) μ, δ 1, δ 2, and κ agonists, respectively, also elicited increases in pial artery diameter and CSF cGMP that were similarly attenuated by LNA. The coadministration of l-Arg (10 −3 M) with LNA partially restored opioid-induced pial artery dilation and associated changes in CSF cGMP whereas d-Arg (10 −3 M) coadministered with LNA did not restore opioid-induced vascular and biochemical changes. These data indicate that NO contributes to opioid-mediated pial artery vasodilation.