PhD Scientific Days 2023

Translational Medicine - Posters O

Effect of CB-1 receptor deficiency on morphological and functional changes in relaxation mechanisms of the female mouse aortic wall

Text of the abstract

Introduction: The endocannabinoid system (ECS) is well known for its psychoactive effects, but it also act on the female reproductive system. Cannabinoids are involved in the regulation of the hypothalamo-pituitary-ovarian axis (HPO) and estrogen production. Estrogens have also been shown to significantly modulate cardiovascular function. In our previous experiments, we have shown increased estrogen-induced relaxation of the abdominal aorta in cannabinoid receptor 1 (CB-1) knock out mice. Therefore, we aimed to investigate the effect of ECS and the role of endothelial factors in the estrogen-induced vascular response.
Aim: To investigate the possible morphological and signaling changes underlying the enhanced estrogen-dependent relaxation observed in CB-1 receptor-deficient animals.
Methods: Our experiments were performed in CB-1 receptor knock out and wild type female mice. After anaesthesia (pentobarbital 50mg/kg ip.), abdominal aortic segments were isolated from the animals for previous myographic and histological as well as immunohistochemical (IHC) measurements in our study. The structure of the vessels investigated by hematoxylin-eosin (HE) and resorcin-fuchsin (RF) stained sections, and proteins involved in the signaling process were examined by immunohistochemical labeling (estrogen receptor (ER), thromboxane receptor (TP) and endothelial nitric oxide synthase (eNOS) and cyclooxygenase 2 (COX-2).
RESULTS: In HE staining, the intima-media ratio of CB-1 KO group was significantly lower compared to the control group (p<0.05). No significant difference in ER receptor and TP receptor density was found between the two groups. COX-2 density was significantly lower in the CB-1 KO group compared to the control group (p<0.05). eNOS density was significantly higher in the CB-1 KO group (p<0.001).
CONCLUSION: CB-1-KO mice are characterized by increased estrogen-induced vasorelaxation, which our results suggest may be associated with increased production of endothelial NO (nitric oxide); presumably associated with decreased levels of the constrictor prostanoids.
Funding: OTKA K116954 & K139231