Modulation of the cardiac autonomic transmission of pithed rats by presynaptic opioid OP 4 and cannabinoid CB 1 receptors

Abstract

We studied the effects of nociceptin, the endogenous ligand of the opioid OP4 receptor, and of two cannabinoid receptor agonists WIN 55,212-2 and CP-55,940 (0.001-1 micromol/kg each) on the neurogenic tachycardia and bradycardia in pithed rats. Electrical stimulation (1 Hz, 1 ms, 50 V for 10 s) of the preganglionic sympathetic nerve fibres and injection of nicotine 2 micromol/kg or isoprenaline 0.5 nmol/kg increased heart rate by about 70 beats/min (bpm) in pithed rats pretreated with atropine 1.5-2 micromol/kg. The electrically induced tachycardia was reduced dose dependently by nociceptin, WIN 55,212-2 and CP-55,940 (by 60, 30 and 20% at the highest dose, respectively). The OP4 and cannabinoid receptor agonists diminished the nicotine- but not the isoprenaline-stimulated increase in heart rate. In pithed rats pretreated with propranolol 3 micromol/kg, vagal stimulation (5 Hz, 1 ms, 15 V for 10 s) or injection of methacholine (5-10 nmol/kg) decreased heart rate by about 30 bpm. Nociceptin, but not WIN 55,212-2 or CP-55,940 decreased the vagal bradycardia dose dependently (the inhibitory effect of 1 micromol/kg was about 40%). Nociceptin failed to modify the methacholine-induced decrease in heart rate. The OP4 receptor antagonists naloxone benzoylhydrazone 5 micromol/kg and/or [Phe1Psi(CH2-NH)Gly2]-nociceptin(1-13)NH2 0.7 micromol/kg, but not the OP(1-3) receptor antagonist naloxone 10 micromol/kg, diminished the inhibitory action of nociceptin on the neurogenic tachycardia and bradycardia. The inhibitory effect of both cannabinoid receptor agonists on the neurogenic tachycardia was abolished by the CB1 receptor antagonist SR 141716 0.1 micromol/kg. The present data suggest that the postganglionic sympathetic nerve fibres innervating the rat heart are endowed with presynaptic opioid OP4 and cannabinoid CB1 receptors, activation of which inhibits the neurogenic tachycardia. The parasympathetic nerve fibres innervating the heart and causing bradycardia are endowed with presynaptic opioid OP4 but not cannabinoid receptors.

Presynaptic cannabinoid CB1 receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

“…Thus, the inhibitory influence of LPS on the neurogenic vasopressor response was abolished by the CB 1 receptor antagonist SR 141716A. The latter drug was used at a dose of 100 nmol kg À1 previously shown to counteract the inhibitory action of the cannabinoid receptor agonists WIN 55,212-2 and CP-55,940 on the neurogenic tachycardia in pithed rats (Malinowska et al, 2001b). SR 141716A has frequently been shown to cause effects opposite to those of cannabinoid receptor agonists and the possibility that this drug abolished the inhibitory effect of LPS on the neurogenic vasopressor response due to a facilitatory effect on this parameter had to be considered.…”

Functional Selectivity of Nociceptin/Orphanin FQ Peptide Receptor Partial Agonists on Cardiovascular and Renal Function

“…Despite their unique and cellular/tissue/system-dependent pharmacological profile, it remains to be established how NOP receptor partial agonists affect cardiovascular and renal function in conscious rats compared with the native ligand N/OFQ. This is of particular interest since NOP receptors that are expressed in both central (brain and spinal cord) and peripheral tissues (vasculature, kidneys, heart, sympathetic, and parasympathetic nerve terminals) (Mollereau and Mouledeous, 2000;Malinowska et al, 2001Malinowska et al, , 2000b) may be affected differently by various classes of NOP receptor ligands (e.g., N/OFQ and NOP receptor partial agonists) to influence cardiovascular and renal function.…”

Methanandamide Allosterically Inhibits in Vivo the Function of Peripheral Nicotinic Acetylcholine Receptors Containing the α7-Subunit

“…Our approach to this first aim, which, in fact, covered a major part of our study, was based on a report by Malinowska et al (2001b). In that investigation, the electrically and NICevoked tachycardic response was determined in pentobarbitone-anesthetized and vagotomized pithed rats treated with atropine, and the operation of presynaptic CB 1 receptors on postganglionic sympathetic nerve fibers in vivo was proven using synthetic cannabinoids to stimulate these receptors.…”

“…All experiments were performed according to Malinowska et al (2001b). They were initiated by the injection of pancuronium (0.8 mol/kg i.v.)…”