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Function of Presynaptic Inhibitory Cannabinoid CB1 Receptors in Spontaneously Hypertensive Rats and Its Modification
Marek Toczek1, Eberhard Schlicker2, Patryk Remiszewski1
1Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicza Str. 2A, 15-222 Białystok, Poland.
International Journal of Molecular Sciences
|January 23, 2024
Summary
Cannabinoid CB1 receptor function in blood pressure regulation differs between hypertensive and normotensive rats. In spontaneously hypertensive rats, CB1 receptor function is preserved when endocannabinoid levels increase.
Area of Science:
- Cardiovascular Physiology
- Neuropharmacology
- Endocannabinoid System
Background:
- Presynaptic cannabinoid CB1 receptors modulate sympathetic nerve activity in blood vessels.
- The role of CB1 receptors in hypertension, particularly in spontaneously hypertensive rats (SHR), requires further elucidation.
- Previous studies suggest altered CB1 receptor function in deoxycorticosterone (DOCA)-salt hypertension.
Purpose of the Study:
- To investigate the function of presynaptic inhibitory cannabinoid CB1 receptors in the sympathetic nerve fibers of resistance vessels in SHR.
- To compare CB1 receptor function in SHR with normotensive Wistar-Kyoto rats (WKY) under basal and stimulated conditions.
- To determine the impact of modulating endocannabinoid tone on CB1 receptor function in hypertension.
Main Methods:
- Induction of diastolic blood pressure (DBP) increase via electrical stimulation of preganglionic sympathetic neurons or phenylephrine injection in pithed rats.
- Administration of cannabinoid receptor agonist (CP55940), endocannabinoid reuptake inhibitor (AM404), CB1 receptor antagonist (AM251), and enzyme inhibitors (MJN110, JZL195, URB597).
- Assessment of DBP changes in response to pharmacological interventions in SHR and WKY.
Main Results:
- Electrically induced DBP increase was inhibited by CP55940 similarly in SHR and WKY, indicating preserved agonist function.
- AM404 inhibited electrically induced DBP increase only in SHR, suggesting enhanced endocannabinoid reuptake inhibition.
- CB1 receptor antagonist AM251 abolished CP55940 effects in both groups. Endocannabinoid degradation blockade (MJN110, JZL195) enhanced CP55940 effects in SHR, indicating better preserved CB1 receptor function with increased endocannabinoid tone.
Conclusions:
- Presynaptic inhibitory CB1 receptor function is model-dependent in hypertension.
- While basal CB1 receptor function is similar in SHR and WKY, it is better preserved in SHR when endocannabinoid tone is elevated.
- Modulation of the endocannabinoid system offers potential therapeutic avenues for managing blood pressure in hypertensive states.
Keywords:
CP55940cannabinoid receptorsendocannabinoidspithed ratpresynaptic receptorsspontaneously hypertensive ratssympathetic systemMore Related Videos
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