Vasopressin modulates cerebrovascular responses to opioids in newborn pigs

Vasopressin receptor blockade has been observed to attenuate the systemic vascular effects of dynorphin. This study was designed to determine the ability of vasopressin to modulate cerebrovascular responses to opioids in newborn pigs equipped with closed cranial windows. Topical dynorphin 13 increased pial arteriolar diameter during normotension (151 +/- 5, 171 +/- 4, 183 +/- 4 and 187 +/- 4 microns for control, 10(-10), 10(-8) and 10(-6) M dynorphin 13, respectively). During hypotension, however, responses to dynorphin 13 were reversed to concentration-dependent decreases in pial arteriolar diameter (184 +/- 3, 169 +/- 4, 165 +/- 4 and 159 +/- 4 microns for control 10(-10), 10(-8) and 10(-6) M dynorphin 13, respectively). Dynorphin 13-induced pial arteriolar dilation was potentiated by the V1 receptor antagonist [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2(o-methyl)-Tyr-AVP] (MEAVP; 5 micrograms/kg i.v.; 14 +/- 1, 22 +/- 1 and 24 +/- 1% vs. 19 +/- 1, 26 +/- 1 and 30 +/- 1% increase for 10(-10), 10(-8) and 10(-6) M dynorphin 13 before and after MEAVP, respectively). In contrast, dynorphin 13-induced constriction during hypotension was markedly reduced by MEAVP (10 +/- 1, 15 +/- 1 and 16 +/- 2% vs. 1 +/- 1, 4 +/- 1 and 9 +/- 1% decrease for 10(-10), 10(-8) and 10(-6) dynorphin 13 before and after MEAVP, respectively). Dynorphin 8 and the synthetic kappa-opioid selective agonist, U5O,488H, elicited similar tone-dependent responses that were modified by MEAVP in a similar fashion.(ABSTRACT TRUNCATED AT 250 WORDS)