CP55940-induced vasorelaxation is endothelial-dependent and mediated by the CB1R through NOS, COX and EDHF pathways in porcine cerebral arteries.

Autor: Morse CJ; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada., Morton JS; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada., Marshall RA; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada., El Karsh Z; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada., Heistad RM; Cell Signalling Laboratory, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada., Laprairie RB; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada., Mousseau DD; Cell Signalling Laboratory, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada., Olver TD; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada. Electronic address: dylan.olver@usask.ca.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2023 Jul; Vol. 148, pp. 104550. Date of Electronic Publication: 2023 May 23.
DOI: 10.1016/j.mvr.2023.104550
Abstrakt: Using swine as an experimental model, we examined whether the cannabinoid receptors (CB1R and CB2R) modulated vasomotor tone in isolated pial arteries. It was hypothesized that the CB1R would mediate cerebral artery vasorelaxation in an endothelial-dependent manner. First-order pial arteries were isolated from female Landrace pigs (age = 2 months; N = 27) for wire and pressure myography. Arteries were pre-contracted with a thromboxane A 2 analogue (U-46619) and vasorelaxation in response to the CB1R and CB2R receptor agonist CP55940 was examined in the following conditions: 1) untreated; 2) inhibition of the CB1R (AM251); or 3) inhibition of the CB2R receptor (AM630). The data revealed that CP55940 elicits a CB1R-dependent relaxation in pial arteries. CB1R expression was confirmed using immunoblot and immunohistochemical analyses. Subsequently, the role of different endothelial-dependent pathways in the CB1R-mediated vasorelaxation was examined using: 1) denudation (removal of the endothelium); 2) inhibition of cyclooxygenase (COX; Naproxen); 3) inhibition of nitric oxide synthase (NOS; L-NAME); and 4) combined inhibition of COX + NOS. The data revealed CB1R-mediated vasorelaxation was endothelial-dependent, with contributions from COX-derived prostaglandins, NO, and endothelium-dependent hyperpolarizing factor (EDHF). Pressurized arteries underwent myogenic curves (20-100 mmHg) under the following conditions: 1) untreated; 2) inhibition of the CB1R. The data revealed CB1R inhibition increased basal myogenic tone, but not myogenic reactivity. As the vascular responses were assessed in isolated pial arteries, this work reveals that the CB1R modulates cerebrovascular tone independently of changes in brain metabolism.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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