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Title: Cardiovascular effects of cannabinoids in normotensive and hypertensive rats
Author: Wheal, Amanda Jane
ISNI:       0000 0001 3566 4884
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2008
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Although cannabinoids cause vasorelaxation of isolated blood vessels, their cardiovascular effects in vivo are complex and may depend on the prevailing experimental conditions or disease states. In this thesis, the regional haemodynamic responses to cannabinoids have been examined in vivo in two rat models of hypertension, in the conscious freelymoving state and under anaesthesia. Parallel in vitro studies were performed in isolated vessels and perfused mesenteric vascular beds. Enhanced vasorelaxation to the endogenous cannabinoid, anandamide, due to an up-regulation of sensory nerve activity, was observed in isolated perfused mesenteric arterial beds from rats chronically treated with L-NAME. In contrast, this enhancement was not seen in isolated mesenteric arterial vessels or in aortic rings, and did not occur in vivo. In conscious rats, the initial bradycardia, renal and mesenteric vasoconstriction, and depressor then pressor responses to anandamide were similar in L-NAME-treated and control rats in vivo, but anandamide caused vasodilatation in the hindquarters vasculature only in control rats. However, in conscious spontaneously hypertensive rats (SHR), but not controls, modest depressor responses to anandamide and the Ii)'nthctic cannabinoid, WIN55212-2, were observed, but were not fully nttrlbutnblc to CHI receptor-mediated vasodilatation. In addition, pressor ro8Jl{J1lIC8 to CBI receptor antagonism occurred only in conscious SHR and WIN hot MIOcioted with vasoconstriction. Furthermore, there was evidence fbr (~UI roceptor-mediated vasoconstriction to anandamide in SHR. Importantly, only in anaesthetised SHR was there evidence for enhanced CBI receptor-mediated vasodilatation, as CHI receptor antagonism caused vasoconstriction and pressor responses. Overall, these in vivo responses suggest a possible up-regulation ofthe endocannabinoid system in SHR, which is most evident under anaesthesia and does not occur in rats made hypertensive by treatment with L-NAME.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available