Role of nitric oxide and opioid receptors in the regulation of blood brain barrier permeability

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We studied on the regulation of blood brain barrier by using wet-dog shakes (WDS) induced by paraquat (PQ) in rats, and obtained the following results.(1) Nitric oxide (NO) and opioid receptorsA non-selective NO synthase (NOS) inhibitor, Nω-nitro-L-arginine (L-NA), suppressed the PQ-induced WDS, although D-NA, its enantiomer which was a less potent inhibitor, did not do so. A selective inhibitor to neuronal NOS, 7-nitroindazole (7-NI), suppressed the WDS as well. L-arginine (L-Arg), the precursor of NO, had no effect on the suppression by L-NA and 7-NI, but naloxone, an antagonist of opioid receptors, abolished the suppression. On the other hand, we found that the administration of PQ into the hippocampus strongly induced WDS. This WDS was strongly suppressed by L-NA. NO production in the hippocampus was increased by PQ. The increase in NO production by PQ was suppressed by L-NA, and this suppression was partly reversed by L-Arg. However, these changes in the hippocampal production of NO appeared after the PQ-induced WDS had occurred and disappeared. These findings suggest that NO plays a minor role in the PQ-induced WDS, and the suppressive effect of NOS inhibitors may be mediated through opioid receptors rather than inhibition of the NO production.(2) Vasopressin (V1) receptorsA non-peptide V1 receptor antagonist, OPC-21268, suppressed the PQ-induced WDS. In contrast, a peptide V1 receptor antagonist, [deamino-PenィイD11ィエD1, O-Me-TyィイD12ィエD1, ArgィイD18ィエD1]-vasopressin had no effect on the WDS. These suggest that V1 receptors may play a minor role in the PQ-induced WDS. The suppressive effect of OPC-21268 might be mediated through a pathway other than V1 receptors.