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.
