Semmelweis University

THE ROLE OF THE ENDOCANNABINOID SYSTEM IN THE REGULATION OF VASCULAR TONE

Bányai Bálint Péter

Theoretical and Translational Medicine Division

Dr. Kellermayer Miklós

SE Élettani Intézet könyvtára

2026-04-28 14:00:00

Kórélettan és transzlációs medicina

Dr. Benyó Zoltán

Dr. Horváth Eszter Mária

Dr. Sára Levente

Dr. Bálint Olga Hajnalka

Dr. Fekete Andrea

Dr. Légrády Péter

Dr. Nemcsik János

Both the endocannabinoid system (ECS) and estrogens play significant roles in cardiovascular control processes. Cannabinoid type 1 receptors mediate acute vasodilator and hypotensive effects, although their role in cardiovascular pathological conditions remains controversial. Estrogens are known to exert cardiovascular protection, particularly in females. This study aimed to explore the impact of ECS on vascular functions and the effects of the phytocannabinoid THC in endotoxemic model, and on the other hand, we also want to investigate the role of CB1R deficiency in healthy female mice. In a 24-hour endotoxemic rat model (E. coli-derived lipopolysaccharide, LPS, 5 mg/kg i.v.) animals were treated with THC (LPS+THC, 10 mg/kg i.p.). The endothelium-dependent relaxation of the thoracic aorta was measured using wire-myography. The molecular mechanisms of the vascular function were evaluated by measuring the density of eNOS, COX–2 and cGMP via immunohistochemistry. The oxidative – nitrative stress status has been defined as the density of oxidative stress marker 4-hydroxynonenal, the density of nitrative stress marker 3-nitrotyrosine, and the density poly(ADP-ribose) polymer. Further experiments were conducted on CB-1R knockout (CB1-R KO) and wild-type (WT) female mice. Abdominal aortas were isolated for histology. Histological analyses included hematoxylin-eosin and resorcin-fuchsin staining, as well as immunostainings for eNOS, COX-2, and estrogen receptors (ERα, ERβ). Results showed that endothelium-dependent relaxation was impaired by LPS but not in the LPS+THC group. THC treatment reduced oxidative-nitrative stress without affecting cGMP and eNOS density, suggesting an anti-inflammatory pathway activation. Histology revealed lower intima/media thickness and COX-2 density, higher eNOS, and lower ER-β density in CB1-R KO mice compared to WT mice. These findings indicate that the absence of CB1Rs in healthy females and the administration of THC in case of infection may have beneficial vascular effects, potentially mediated through anti-inflammatory pathways and enhanced endothelial NO utilization