title: Cardiovascular effects of microinjection of dynorphin fragments into the nucleus of the solitary tract (NTS) are mediated by non-opioid mechanisms.
abstract: The nucleus of the solitary tract (NTS) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of dynorphin A-(1-13), dynorphin A-(1-17) and dynorphin A-(2-17) microinjected into the NTS on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV) and left ventricular stroke work (LVSW) following hemorrhage in conscious rats. Following fixed-volume hemorrhage (8 ml/300 g), microinjection of dynorphin A-(2-17) (6 nmol), which is inactive at opioid receptors, into the NTS significantly attenuated the recovery of CO, SV and LVSW following hemorrhage when compared to those animals receiving a microinjection of normal saline (NS) vehicle into the NTS (P < 0.01). NTS microinjection of dynorphin A-(2-17) also increased HR following hemorrhage when compared with the NS group (P < 0.05). No significant effects were observed on CO, SV and LVSW following NTS microinjection of the kappa-opioid agonists, dynorphin A-(1-13) and dynorphin A-(1-17), although dynorphin A-(1-13) microinjection increased HR following hemorrhage when compared with control animals (P < 0.05). Microinjection of all three peptide fragments had no significant effect on MAP when compared with MAP of the control group following hemorrhage. The results of this study suggest that dynorphin A-(2-17) in the NTS can attenuate the compensatory cardiovascular responses to hemorrhage, perhaps via a non-opioid mechanism.
authors.affiliation: Division of Neurosurgery, University of Pennsylvania, Philadelphia 19104.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins; C082245:dynorphin (2-17)