Tonic inhibitory control exerted by opioid peptides in the paraventricular nuclei of the hypothalamus on regional hemodynamic activity in rats

Systemic and regional cardiovascular changes were measured following bilateral microinjection of specific and selective opioid‐receptor antagonists into the paraventricular nuclei of the hypothalamus (PVN) of awake, freely moving rats. PVN microinjection of increasing doses of the specific opioid antagonist naloxone – methiodide (1 – 5.0 nmol), or a selective μ‐opioid receptor antagonist, β‐funaltrexamine (0.05 – 0.5 nmol), evoked important cardiovascular changes characterized by small and transient increases in heart rate (HR) and mean arterial pressure (MAP), vasoconstriction in renal and superior mesenteric vascular beds and vasodilation in the hindquarter vascular bed. No significant cardiovascular changes were observed following PVN administration of the highly selective δ‐opioid‐receptor antagonist, ICI 174864 (0.1 – 1 nmol), or the selective κ‐opioid‐receptor antagonist, nor ‐binaltorphine (0.1 – 1 nmol). Most of the cardiovascular responses to naloxone (3 nmol) and β‐funaltrexamine (0.5 nmol) were attenuated or abolished by an i.v. treatment with a specific vasopressin V 1 receptor antagonist. These results suggest that endogenous opioid peptides and μ‐type PVN opioid receptors modulate a tonically‐active central depressor pathway acting on systemic and regional haemodynamic systems. Part of this influence could involve a tonic inhibition of vasopressin release.British Journal of Pharmacology (2002) 136 , 753–763; doi: 10.1038/sj.bjp.0704780