Chronic Blockade of Hippocampal Kappa Receptors Increases Arterial Pressure in Conscious Spontaneously Hypertensive Rats but Not in Normotensive Wistar Kyoto Rats

Abstract

Previous studies in this laboratory have shown that dynorphins acting on hippocampal kappa opioid receptors in rat brain exert a restraining influence on arterial blood pressure and that a relative deficiency of their production in the spontaneously hypertensive rat (SHR) may be involved in SHR hypertension. Kappa receptor blockade should therefore exacerbate hypertension in SHR. We explored the latter possibility by chronic unilateral infusion of nor-binaltorphimine dihydrochloride (nor-BNI), a selective kappa receptor antagonist, into the right dorsal hippocampus of conscious SHR and normotensive Wistar-Kyoto (WKY) controls over a 14 day period. Additional controls consisted of similar hippocampal infusions of equivalent volumes of drug vehicle in both rat strains. Mean arterial pressure (MAP) and heart rates (HR) were determined in each animal once daily by the tail cuff method during this period. Nor-BNI induced a sustained increase in the basal high level of MAP in SHR from 132 +/- 8 to 150 +/- 10 mmHg throughout the 14 days and an increased HR from 427 +/- 17 to 477 +/- 30 on day 3 to 5 following the drug. By contrast, nor-BNI had no significant effects on either MAP or HR in WKY rats and control infusions of drug vehicle were similarly without effect in both strains. The results support our previous suggestion that the kappa opioid system of the hippocampus ordinarily restrains arterial blood pressure in SHR since prolonged hippocampal kappa receptor blockade results in augmented hypertension in this strain.

The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress

“…Consistently, nor-BNI (4 nmol/kg/h) administered unilaterally into the hippocampus for 14 days increased the BP of SHR rats from baseline 136 ± 11 to 150 ± 10 mmHg with a significant peak on day 7 of the treatment. This was alongside the complete absence of any effect of nor-BNI on BP in control WKY rats [ 50 ]. Importantly, more effective blockage of κ opioid receptors resulted in an apparent increase in BP both in SHR and normotensive rats has been achieved after bi-hippocampal microinjection of antisense oligodeoxynucleotide to the rat κ opioid receptor twice a day for 5 days [ 51 ].…”

“…Importantly, more effective blockage of κ opioid receptors resulted in an apparent increase in BP both in SHR and normotensive rats has been achieved after bi-hippocampal microinjection of antisense oligodeoxynucleotide to the rat κ opioid receptor twice a day for 5 days [ 51 ]. Certainly, bilateral treatment of the specific brain area inducing hypertension in both rat strains appeared to be more effective than the unilateral approach [ 50 ]. The same BP-increasing effect was observed when nor-BNI (10 nmol/0.5 mL twice a day for 13 days) was administrated bilaterally to the hippocampus in both normotensive rats and animals with social isolation-induced hypertension [ 52 ].…”