Blockade of dorsal hippocampal kappa-opioid receptors increases blood pressure in normotensive and isolation-induced hypertensive rats.

Previous research in our laboratory has established a restraining role of the hippocampal kappa-opioid receptor system in the neural control of blood pressure. Chronic or acute hippocampal administration of kappa-agonists has been shown to reduce blood pressure. Isolation of male Sprague-Dawley rats provokes an increase in blood pressure, which has been proposed as a valid model of mild emotionally induced hypertension. It was the purpose of this study to investigate the blood pressure effects of dorsal hippocampal administration of nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist; in conscious male Sprague-Dawley rats subjected to isolation-induced hypertension. Chronic bi-hippocampal microinjection of nor-BNI (10 nmol per side, twice a day for 13 days) caused increases in systolic blood pressure in grouped rats from a mean of 125 to 148 mmHg, and in isolated rats from a mean of 125 to 151 mmHg. This hypertension was similar in magnitude to the increase observed after rats were isolated for 7 days and treated with vehicle in a similar fashion (mean systolic blood pressure 144 mmHg). The increases in blood pressure were accompanied by bradycardia. No significant responses were seen in the blood pressure of grouped rats treated with vehicle. The hypotensive response to a single hippocampal microinjection of the kappa-agonist U62, 066E (10 or 20 nmol) was prevented in anesthetized rats treated previously with nor-BNI, indicating that in the nor-BNI treated rats there was effective blockade of dorsal hippocampal receptors. These data suggest that the rat hippocampal kappa-opioid receptor system and the endogenous neuropeptide dynorphin may be involved in the central neural regulation of blood pressure.