Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin

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Abstract
Experiments were conducted (i) to determine the hemodynamic (blood pressure and heart rate) responses of conscious rats following intrathecal (IT) administration of endogenous prodynorphin-derived opioids into the lower thoracic space, (ii) to identify the receptors involved in mediating their cardiovascular responses, and (iii) to reveal any possible hemodynamic interactions with the neuropeptide arginine vasopressin. Male Sprague–Dawley rats were surgically prepared with femoral arterial and venous catheters as well as a spinal catheter (into lower thoracic region, T9–T12). After recovery, hemodynamic responses were observed in conscious rats for 5 – 10 min after IT injections of artificial cerebrospinal fluid (CSF) solution, prodynorphin-derived opioids (dynorphin A, dynorphin B, dynorphin A (1 – 13), dynorphin A (1 – 10), α- and β-neoendorphin, leucine enkephalin (LE), methionine enkephalin (ME), arginine vasopressin (AVP), or norepinephrine (NE)). IT injections of AVP (10 or 20 pmol), dynorphin A (1 – 13), or dynorphin A (10 – 20 nmol) caused pressor effects associated with a prolonged and significant bradycardia. Equimolar (20 nmol) concentrations of LE, ME, α- and β-neoendorphin, and dynorphin A (1 – 10) caused no significant blood pressure or heart rate changes. Combined IT injections of dynorphin A (1 – 13) and AVP caused apparent additive pressor effects when compared with the same dose of either peptide given alone. IT infusion of the specific AVP–V1 antagonist d(CH2)5Tyr(Me)AVP before subsequent IT AVP, dynorphin A (1 – 13), or NE administration inhibited only the subsequent pressor responses to AVP. The x-opioid antagonist (Mr2266) infused IT blocked the pressor actions of subsequent dynorphin A administration and not AVP or NE. These results indicate that dynorphin A and dynorphin A (1 – 13), in the doses used, given IT to conscious rats evoked pressor and bradycardic responses. The pressor actions of dynorphin A appear to be mediated by spinal x-opioid receptors and are independent of interaction with spinal AVP–V1 receptors.Key words: prodynorphin-derived peptides, arginine vasopressin, intrathecal administration, hemodynamic effects, specific receptor-mediated responses.