Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA-salt hypertensive rats

Marek Toczek; Eberhard Schlicker; Emilia Grzęda; Barbara Malinowska

doi:10.1016/j.lfs.2015.03.022

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA-salt hypertensive rats

Life Sci. 2015 Oct 1:138:78-85. doi: 10.1016/j.lfs.2015.03.022. Epub 2015 Apr 25.

Authors

Marek Toczek¹, Eberhard Schlicker², Emilia Grzęda¹, Barbara Malinowska³

Affiliations

¹ Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicz Str. 2A, 15-222 Białystok, Poland.
² Department of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
³ Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicz Str. 2A, 15-222 Białystok, Poland. Electronic address: bmalin@umb.edu.pl.

PMID: 25921770
DOI: 10.1016/j.lfs.2015.03.022

Abstract

Aims: This study was performed to examine whether hypertension affects the sympathetic transmission to resistance vessels of pithed rats via inhibitory presynaptic cannabinoid CB1 receptors and whether endocannabinoids are involved in this response.

Materials and methods: We compared uninephrectomised rats rendered hypertensive by high salt diet and deoxycorticosterone acetate (DOCA) injections with normotensive animals (uninephrectomy only). Experiments were performed on vagotomised and pithed animals. Increases in diastolic blood pressure (DBP) were induced four times (S1-S4) by electrical stimulation or phenylephrine injection.

Key findings: Electrical stimulation (0.75Hz, 1ms, 50V, 5 impulses) of the preganglionic sympathetic nerve fibres innervating the blood vessels more strongly increased DBP in normotensive than in DOCA-salt rats. Phenylephrine (0.01μmol/kg) induced similar increases in DBP in both groups. The cannabinoid receptor agonist CP55940 (0.01-1μmol/kg) did not modify the rises in DBP induced by phenylephrine. However, it inhibited the electrically stimulated increases in DBP, more strongly in DOCA-salt than in normotensive animals (maximally by 50 and 30%, respectively). The effect of CP55940 was attenuated by the CB1 antagonist AM251 (3μmol/kg). AM251 enhanced the neurogenic vasopressor response during S4 by itself in hypertensive rats only. URB597 (3μmol/kg), which inhibits degradation of the endocannabinoid anandamide, did not modify the electrically stimulated increases in DBP.

Significance: The function of inhibitory presynaptic CB1 receptors on sympathetic nerves is enhanced in DOCA-salt hypertensive rats. Thus, the CB1 receptor-mediated inhibition of noradrenaline release from the sympathetic nerve fibres innervating the resistance vessels might play a protective role in hypertension.

Keywords: 11-Deoxycorticosterone acetate (PubChem CID: 3001); AM251 (PubChem CID: 2125); CP55940; CP55940 (PubChem CID: 104895); Cannabinoid receptors; DOCA–salt hypertension; Phenylephrine hydrochloride (PubChem CID: 5284443); Pithed rat; Presynaptic receptors; Prostaglandin F(2α) (PubChem CID: 5282415); URB597 (PubChem CID: 1383884).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzamides / pharmacology
Blood Pressure / drug effects
Cannabinoid Receptor Agonists / pharmacology
Cannabinoid Receptor Antagonists / pharmacology
Carbamates / pharmacology
Desoxycorticosterone Acetate
Hypertension / chemically induced
Hypertension / physiopathology*
Male
Nephrectomy
Phenylephrine / pharmacology
Rats
Rats, Wistar
Receptor, Cannabinoid, CB1 / drug effects*
Receptors, Presynaptic / drug effects*
Sodium, Dietary / adverse effects
Sympathetic Nervous System / drug effects*

Substances

Benzamides
Cannabinoid Receptor Agonists
Cannabinoid Receptor Antagonists
Carbamates
Receptor, Cannabinoid, CB1
Receptors, Presynaptic
Sodium, Dietary
cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
Phenylephrine
Desoxycorticosterone Acetate