Role of cyclic nucleotides in vasopressin-induced piglet pial artery dilation and opioid release

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 (R(p))-8-bromo-(Br)-cAMPs and (R(p))-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 (R(p))-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 (R(p))-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 (R(p))-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 (R(p))-8-Br-cGMPs, respectively, n = 7), CSF opioid concentrations increased with topical vasopressin and these increases were attenuated by (R(p))-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 (R(p))-8-Br-cAMPs. Similarly, vasopressin-induced CSF methionine enkephalin and leucine enkephalin release was attenuated in the presence of (R(p))-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.