Translational Medicine III.
Zsolt Vass1, Anikó Balogh1, Gellért Karvaly2, Krisztián Kovács2, Barna Vásárhelyi2, György Nádasy3, László Hunyady3,4, Gabriella Dörnyei1, Mária Szekeres1,3
1Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest
2Department of Laboratory Medicine, Semmelweis University, Budapest
3Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest;
4Institute of Enzymology, Eötvös Loránd Research Network, Research Centre for Natural Sciences, Budapest
Introduction: There is an important interplay between the endocannabinoid system (ECS) and the female reproductive system. Cannabinoids inhibit the release of gonadotropin releasing hormone (GnRH) by altering the regulation of hypothalamic-pituitary axis (HPA) and estrogen production. Also, estrogens have been shown to significantly modulating cardiovascular functions.
Aims: we aimed to study the impact of ECS on estrogen-induced vasomotor function and estrogen levels.
Methods: Experiments were performed on CB1 receptor knockout (CB1R-KO) and wild-type (WT) female mice. Plasma samples were taken to determine estrogen metabolite levels. Isolated abdominal aortic rings were mounted in a myograph. Contractile responses to phenylephrine (Phe) and relaxation to acetylcholine (Ach) were obtained to test vasomotor functions. Vasomotor effects of estradiol (ED) were obtained in control conditions and repeated in the presence of inhibitors of cyclooxygenase (COX, indomethacin) and nitric oxide synthase (NOS, nitro-L-arginine).
Results: Plasma conjugated estradiol levels were higher (p<0.05) in female CB1R-KO mice compared to WT. ED increased relaxation of aorta isolated from CB1R-KO mice (p<0.05) compared to that of WT mice, which effect was attenuated by NOS-inhibition. COX-inhibition slightly increased ED-relaxation in WT mice.
Conclusion: CB1R-KO mice are characterized by increased ED-induced vasorelaxation, which can be associated with an increased utilization of endothelial NO and altered prostanoid production. CB1R-KO mice had higher conjugated ED levels indicating a depressed cannabinoid-dependent inhibition on HPA. The increased ED dependent vasorelaxation in the absence of CB1 receptors may potentially contribute to the antihypertensive action of cannabinoids.
Funding: Hungarian National Grants OTKA116954 and 139231, ÚNKP-22-3-II-SE-6