Mária Szekeres

The negative cardiovascular effects of polycystic ovary syndrome (PCOS) and vitamin D deficiency (VDD) have been discussed previously; however, the sex differences between PCOS females and males are not yet known. Our aim was to investigate the effect of PCOS and VDD in the carotid artery of male and female Wistar rats. Females were treated with transdermal testosterone (Androgel) for 8 weeks, which caused PCOS. VDD and vitamin D supplementation were accomplished via diet. The carotid arteries’ contraction and relaxation were examined using myography. Receptor density was investigated using immunohistochemistry. In PCOS females, angiotensin receptor density, angiotensin II-induced contraction, androgen receptor optical density, and testosterone-induced relaxation increased. The increased contractile response may increase cardiovascular vulnerability in women with PCOS. As an effect of VDD, estrogen receptor density increased in all our groups, which probably compensated for the reduced relaxation caused by VDD. Testosterone-induced relaxation was decreased as a result of VDD in males and non-PCOS females, whereas this reduction was absent in PCOS females. Male sex is associated with increased contraction ability compared with non-PCOS and PCOS females. VDD and Androgel treatment show significant gender differences in their effects on carotid artery reactivity. Both VDD and PCOS result in a dysfunctional vascular response, which can contribute to cardiovascular diseases.

Both the endocannabinoid system (ECS) and estrogens have significant roles in cardiovascular control processes. Cannabinoid type 1 receptors (CB1Rs) mediate acute vasodilator and hypotensive effects, although their role in cardiovascular pathological conditions is still controversial. Estrogens exert cardiovascular protection in females. We aimed to study the impact of ECS on vascular functions. Experiments were performed on CB1R knockout (CB1R KO) and wild-type (WT) female mice. Plasma estrogen metabolite levels were determined. Abdominal aortas were isolated for myography and histology. Vascular effects of phenylephrine (Phe), angiotensin II, acetylcholine (Ach) and estradiol (E2) were obtained and repeated with inhibitors of nitric oxide synthase (NOS, Nω-nitro-L-arginine) and of cyclooxygenase (COX, indomethacin). Histological stainings (hematoxylin-eosin, resorcin-fuchsin) and immunostainings for endothelial NOS (eNOS), COX-2, estrogen receptors (ER-α, ER-β) were performed. Conjugated E2 levels were higher in CB1R KO compared to WT mice. Vasorelaxation responses to Ach and E2 were increased in CB1R KO mice, attenuated by NOS-inhibition. COX-inhibition decreased Phe-contractions, while it increased Ach-relaxation in the WT group but not in the CB1R KO. Effects of indomethacin on E2-relaxation in CB1R KO became opposite to that observed in WT. Histology revealed lower intima/media thickness and COX-2 density, higher eNOS and lower ER-β density in CB1R KO than in WT mice. CB1R KO female mice are characterized by increased vasorelaxation associated with increased utilization of endothelial NO and a decreased impact of constrictor prostanoids. Our results indicate that the absence or inhibition of CB1Rs may have beneficial vascular effects.