INFLUENCE OF ENDOTHELIAL CANNABINOID 1 RECEPTOR ACTIVATION ON CEREBROVASCULAR REGULATION IN SWINE
| dc.contributor.advisor | Olver, Dylan T | |
| dc.contributor.advisor | Mousseau, Darrell | |
| dc.contributor.committeeMember | Chicoine, Al | |
| dc.contributor.committeeMember | Unniappan, Suraj | |
| dc.contributor.committeeMember | Totosy de Zepetnek, Julia | |
| dc.creator | Morse, Cameron J | |
| dc.date.accessioned | 2021-09-29T21:52:40Z | |
| dc.date.available | 2023-09-29T06:05:07Z | |
| dc.date.created | 2021-09 | |
| dc.date.issued | 2021-09-29 | |
| dc.date.submitted | September 2021 | |
| dc.date.updated | 2021-09-29T21:52:40Z | |
| dc.description.abstract | Cannabinoid receptors 1 & 2 (CB1R & CB2R) are present throughout the cardiovascular system and evidence indicates that CB1R activation causes vasodilation in peripheral vascular beds. However, it remains unclear what the direct effects of CB1R or CB2R activation are in cerebral arteries. The present study tested the hypothesis that CB1R and not CB2R receptor activation elicits endothelial-dependent vasorelaxation in the cerebrovasculature. Female Landrace pigs (age=2 months; N=16) were euthanized, their brains were harvested, and pial arteries branching from the middle cerebral artery were isolated for wire myography. Arteries were pre-contracted with a thromboxane A2 analogue (U-46619; 1x10-6 M to 1x10-4 M). Thereafter, vasorelaxation in response to a dual CB1R & CB2R receptor agonist CP55940 (3x10-11 M to 1x10-6 M; half log doses) was examined under the following conditions: 1) untreated; 2) CB1R blockade (AM251; 1x10-7 M); or 3) CB2R receptor blockade (AM630; 1x10-7 M). The data revealed that CP55940 elicits a CB1Rdependent relaxation in cerebral arteries. Subsequently, to determine the role of different endothelial-dependent pathways, CB1R-mediated vasorelaxation was examined under the following conditions: 1) inhibition of nitric oxide synthase (NOS) using L-NAME (3x10-4 M; reveals contributions from nitric oxide); 2) inhibition of in a cyclooxygenase (COX) using Naproxen (3x10-4 M; reveals contributions from prostaglandins); 3) combined NOS and COX inhibition (reveals contributions from endothelial hyperpolarizing factor); and 4) endothelial removal (denudation of the artery; reveals total contribution of the endothelium). These data demonstrated that CB1R-mediated vasorelaxation was attenuated by NOS inhibition and the magnitude of this effect was increased with the combination of NOS + COX inhibition as well as endothelial removal (P<0.05). However, reductions in vasorelaxation during COX inhibition alone only approached significance (P=0.07). Overall, the data indicate CB1R-mediated vasorelaxation is endothelial-dependent and involves contributions from multiple dilatory pathways. Understanding how the CBRs modulate cerebrovascular function is critical when evaluating the short-term and long-term physiological effects, safety and prescriptive use of cannabis and cannabinoids in any clinical context. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/13632 | |
| dc.subject | Vascular Biology | |
| dc.subject | Cerebrovascular regulation | |
| dc.subject | Cannabis | |
| dc.title | INFLUENCE OF ENDOTHELIAL CANNABINOID 1 RECEPTOR ACTIVATION ON CEREBROVASCULAR REGULATION IN SWINE | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.terms | 2023-09-29 | |
| thesis.degree.department | Veterinary Biomedical Sciences | |
| thesis.degree.discipline | Veterinary Biomedical Sciences | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |