PhD Scientific Days 2023

Health Sciences II.

Physiological Significance of the Endocannabinoid System and its Role in Hypertension

Text of the abstract

Introduction: The endocannabinoid system (ECS) regulates cell proliferation, differentiation, and apoptosis. Endocannabinoids (eCBs) are produced primarily in the central nervous system and affect many functions of the body. eCBs are also synthesised in peripheral tissues (e.g. heart, blood cells, adipose tissue, muscles) and affect both energy balance and blood circulation. The role of ECS has also been demonstrated in a number of pathological processes (cardiovascular /CV/ diseases, obesity, diabetes, tumour formation). The main target of action is the cannabinoid CB1 receptor (CB1R), its density is altered in CV diseases, raising the therapeutic potential of ECS modulation. Angiotensin II (Ang II) plays a role in many forms of hypertension. We have previously shown that the vasoconstrictor effect of Ang II is attenuated by endocannabinoids through activation of CB1R.

Aims: We investigated the role of CB1 receptors in the development of Ang II-induced hypertension.

Method: Our experiments were performed in male C57BL/6N, CB1R gene-deficient (CB1-/-) and wild-type (WT, CB1+/+) mice. A continuous delivery of Ang II (800 ng/kg/min) was provided in mice for two weeks by subcutaneous osmotic minipump implantation. Animals were anaesthetized (Euthasol 50 mg/kg ip), their blood pressure (MAP) was measured invasively and aortic tissue samples from the animals were isolated and placed in 4% paraformaldehyde. The samples were subjected to orcein histochemical staining and elastin density of the vessel wall was determined.

Results: Two weeks of Ang II infusion in anaesthetized mice significantly increased MAP (W control: 74.2±6 mmHg, Ang II-treated: 117.1±12 mmHg, p<0.05). Using orcein immunohistochemistry, we showed that optical density (OD) in the aorta of Ang II-infused CB1+/+ mice was lower than in normotensive mice (p<0.05), indicating a reduction in the proportion of elastic fibres in Ang II-induced hypertension. However, the reduced OD in hypertension was enhanced in the absence of CB1 receptors (p<0.05).

Conclusion: Our results suggest that the impaired vascular function observed in Ang II-induced hypertension is mediated in part by CB1R receptors, which may open up new therapeutic strategy by selectively blocking CB1R activity.

Funding: OTKA K116954, K139231; ÚNKP22-3-II-SE-6

Keywords: endocannabinoid system, CB1 receptor, hypertension, angiotensin II, immunohistochemistry