6-cyano-7-nitroquinoxaline-2-3-dione and dynorphin-(1-8)

We previously demonstrated a centrally mediated hypotensive effect of dynorphin A(1-8) (Dyn) in conscious spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats, by intrahippocampal injection. The effect was due to kappa-opioid receptor activation. L-Glutamate (Glu) injected similarly in the same hippocampal sites also produced hypotension. The neural relation between Dyn and Glu responses was unclear. In the present study, using conscious SHR and WKY rats, we determined whether the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) and the Glu NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP-5) had the ability to block the hypotensive effects of intrahippocampal Glu and Dyn, respectively. Block of the Glu response by nor-BNI or of the Dyn response by the N-methyl-D-aspartate (NMDA) receptor blocker might indicate that the Dyn- and Glu-releasing neurons are connected in series in hippocampus. A lack of cross-blocking activity might indicate that Dyn- and Glu-activated systems operate independently in cardiovascular control. The results demonstrated that intrahippocampal nor-BNI antagonized the depressor responses subsequent to Dyn but not those to Glu injected unilaterally in the same hippocampal areas. Similarly, the NMDA receptor blocker antagonized Glu but not Dyn hypotension. Neither Dyn nor Glu responses were blocked by a non-NMDA subclass receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Blood Pressure; Drug Interactions; Dynorphins; Glutamic Acid; Heart Rate; Injections, Intraventricular; Male; Peptide Fragments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Glutamate; Receptors, Opioid, kappa; Species Specificity