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Title: Vasorelaxant actions of cannabinois in the rat
Author: Ho, W. S. V.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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The vasorelaxant activities of cannabinoids were investigated in isolated segments of the left anterior descending coronary artery, and the third generation of superior mesenteric artery, of the rat. The well-known endocannabinoid anandamide caused endothelium-independent relaxation of precontracted coronary arteries by a novel mechanism that involved activation of large conductace Ca2+ -activated K+ channels (BKca) but was apparently independent of the cannabinoid CB1 and CB2 receptors or production of vasoactive metabolites. Interestingly, although anandamide is known to be an agonist of the vanilloid VR1 receptor, and activation of these receptors relaxed coronary artery, inhibitors of the VR1 receptor system did not affect anandamide-induced relaxation in this artery. The mechanisms by which anandamide increases BKCa activity remain unclear, however, it is unlikely that a direct interaction of anandamide with BKCa is involved. There is evidence that the synthetic cannabinoid R-(+)-WIN 55,212-2 also relaxes coronary arteries via mechanisms similar to those of anandamide. In the rat mesenteric artery, while anandamide relaxations were also independent of the endothelium, the major relaxant mechanism of anandamide is activation of VR1 receptors. However, additional mechanism including inhibition of Ca2+ influx to the vascular smooth muscle also play a role, indicating that the vasorelaxant actions of anandamide are complex. In fact, reduction of Ca2+ influx, perhaps via voltage-gated Ca2+ channels in the smooth muscle, formed the basis of the relaxation to the synthetic cannabinoids JWH 015 and R-(+)-WIN 55,212-2 in the mesenteric artery. However, as for rat coronary artery, there was no substantial evidence supporting the presence of CB1 or CB2 receptors, as classically defined, in the smooth muscle rat mesenteric arteries. Further studies using electrical field stimulation of mesenteric arteries, nevertheless, revealed that CB1-like receptors might be present in the prejunctional sympathetic nerve terminals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available