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Cardiovascular effects of cannabinoids in conscious spontaneously hypertensive rats
Author(s) -
Wheal A J,
Bennett T,
Randall M D,
Gardiner S M
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707410
Subject(s) - cannabinoid receptor , anandamide , endocannabinoid system , cannabinoid , medicine , endocrinology , agonist , vasodilation , depolarization induced suppression of inhibition , pharmacology , receptor
Background and purpose: In anaesthetized spontaneously hypertensive rats (SHR), there is evidence for up‐regulation of cannabinoid (CB 1 ) receptors: antagonism of CB 1 receptors causes a rise in blood pressure, and administration of the endocannabinoid, anandamide, or inhibition of anandamide degradation causes hypotension. These findings have led to the suggestion that the endocannabinoid system may be a therapeutic target in hypertension. However, since the cardiovascular responses to cannabinoids are substantially influenced by anaesthesia, the purpose of this study was to assess regional haemodynamic responses to cannabinoid receptor stimulation and inhibition in conscious SHR. Experimental approach: Cardiovascular responses to i.v. administration of anandamide, the cannabinoid receptor agonist, WIN 55212‐2, and the CB 1 receptor antagonist, AM 251, were measured in male SHR, Wistar Kyoto rats and outbred Wistar rats, chronically instrumented for recording renal, mesenteric and hindquarters haemodynamics in the conscious, freely‐moving state. Key results: Hypotensive responses to anandamide and WIN 55212‐2 only occurred in SHR, but these were relatively modest and not associated with CB 1 receptor‐mediated vasodilatation. In SHR only, anandamide caused bradycardia, which was inhibited by AM 251. Furthermore, a pressor response to CB 1 receptor antagonism occurred only in SHR, but was not associated with vasoconstriction. Moreover, there was some evidence for CB 1 receptor‐mediated vasoconstrictor actions of anandamide in SHR, which was not seen in the normotensive strains. Conclusions and implications: The results are consistent with activation of CB 1 receptors in SHR by endogenous ligands exerting an antihypertensive effect, but the findings do not indicate enhanced CB 1 receptor‐mediated vasodilator mechanisms in SHR. British Journal of Pharmacology (2007) 152 , 717–724; doi: 10.1038/sj.bjp.0707410 ; published online 13 August 2007