title: Role of cyclic nucleotides in vasopressin-induced piglet pial artery dilation and opioid release.
abstract: It has previously been observed that the opioids methionine enkephalin and leucine enkephalin contribute to hypoxia-induced pial artery dilation in the piglet. It has also been demonstrated that vasopressin elicits pial artery dilation and contributes to hypoxia-induced pial dilation both directly and indirectly through the release of the above opioids. The present study was designed to investigate the role of cyclic nucleotides in this vasopressin-induced pial artery dilation and opioid release in newborn piglets equipped with a closed cranial window. Pial artery diameter and cortical periarachnoid cerebrospinal fluid (CSF) opioid and cyclic nucleotides were measured after topical application of vasopressin (40, 400, and 4000 pg/mL). Opioid levels and pial diameter were examined in the absence and presence of (Rp)-8-bromo-(Br)-cAMPs and (Rp)-8-Br-cGMPs, purported cAMP and cGMP antagonists, respectively. Periarachnoid cortical CSF cAMP concentration increased in response to topical vasopressin (1048 +/- 22, 1199 +/- 51, 1334 +/- 61 and 1453 +/- 59 fmol/mL for control, 40, 400, and 4000 pg/mL vasopressin, respectively, n = 9). Vasopressin elicited pial artery dilation, which was attenuated by (Rp)-8-Br-cAMPs (14 +/- 1, 22 +/- 1, and 29 +/- 2 versus 8 +/- 1, 12 +/- 2, and 18 +/- 2% dilation for 40, 400, 4000 pg/mL vasopressin, before and after (Rp)-8-Br-cAMPs, respectively, n = 7). Similarly, vasopressin-induced pial artery dilation was accompanied by elevated CSF cGMP and this dilation was attenuated in the presence of (Rp)-8-Br-cGMPs (13 +/- 1, 21 +/- 1, and 29 +/- 2 versus 5 +/- 1, 9 +/- 1, and 12 +/- 1% dilation for 40, 400, and 4000 pg/mL vasopressin before and after (Rp)-8-Br-cGMPs, respectively, n = 7). CSF opioid concentrations increased with topical vasopressin and these increases were attenuated by (Rp)-8-Br-cAMPs. CSF methionine enkephalin concentrations were 1193 +/- 60, 1530 +/- 63, 1937 +/- 89, and 2422 +/- 104 versus 1032 +/- 25, 1185 +/- 261, 1337 +/- 31, and 1519 +/- 44 pg/mL for control, 40, 400 and 4000 pg/mL vasopressin before and after (Rp)-8-Br-cAMPs. Similarly, vasopressin-induced CSF methionine enkephalin and leucine enkephalin release was attenuated in the presence of (Rp)-8-Br-cGMPs. These data show that both cAMP and cGMP contribute to vasopressin-induced pial artery dilation and the release of the opioids methionine enkephalin and leucine enkephalin.
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Rossberg
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D004723:Endorphins / Q000378:metabolism*; D005260:Female; D008297:Male; D009712:Nucleotides, Cyclic / Q000502:physiology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D004723:Endorphins; D009712:Nucleotides, Cyclic; D014665:Vasodilator Agents; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D006152:Cyclic GMP