Key result
Fulvestrant cuts vascular β1- and β3-adrenoceptor mRNA ~50% and impairs β-adrenergic vasodilation in female rats.
Why the study?
The role of oestrogen receptors in maintaining enhanced female β-adrenergic vascular relaxation and the capacity of sex hormone exposure to reprogram vascular β-adrenoceptor expression were incompletely understood.
Does oestrogen receptor modulation alter vascular β-adrenoceptor expression and adrenergic vascular tone in rats and human vessels?
Does oestrogen receptor modulation alter vascular β-adrenoceptor expression and adrenergic vascular tone in rats and human vessels?
p-value: p=<0.05
Oestrogen receptor activation maintains a female-like β-adrenergic vascular profile by upregulating β₁- and β₃-adrenoceptors, providing a mechanism for sex-specific regulation of vascular tone.
Oestrogen receptors may sustain female vascular β-adrenergic tone in rats; hypothesis-generating for human sex differences.
Sex differences in vascular adrenergic responsiveness contribute to differential regulation of vascular tone. Female vessels exhibit enhanced β-adrenergic relaxation compared with males, but the role of oestrogen receptors in maintaining this phenotype and the capacity of sex hormone exposure to reprogram vascular β-adrenoceptor expression remain incompletely understood. Thoracic aorta and mesenteric arteries from Wistar Kyoto rats were examined following pharmacological oestrogen receptor inhibition or cross-sex hormone treatment. Vascular reactivity was assessed using wire myography, and β₁-, β₂-, and β₃-adrenoceptor mRNA expression was quantified by qPCR. Oestrogen receptor blockade with fulvestrant enhanced norepinephrine-induced vasoconstriction and reduced β-adrenergic relaxation in both conduit and resistance arteries. These functional alterations were accompanied by an approximately 50% reduction in β₁- and β₃-adrenoceptor mRNA expression, whereas β₂ expression remained unchanged. Conversely, oestrogen treatment in males attenuated vasoconstriction, enhanced β-adrenergic relaxation, and increased β₁- and β₃-adrenoceptor expression, while testosterone treatment in females had no effects. Despite pronounced vascular changes, arterial blood pressure remained unaltered. Analysis of human aorta, carotid, iliac, and mammary arteries revealed consistently higher β₁- and β₃-adrenoceptor mRNA expression in women compared with men. Oestrogen receptor inhibition reduces vascular β₁- and β₃-adrenoceptor expression and impairs β-adrenergic vasodilation, thereby shifting adrenergic vascular responses towards enhanced constriction. Conversely, oestrogen exposure reprogrammes the male vascular phenotype towards a female-like β-adrenergic profile. These findings identify an oestrogen receptor–dependent β₁/β₃-adrenoceptor axis as a conserved mechanism underlying sex-specific regulation of vascular tone.
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Riedel et al. (2026) studied Sex differences in vascular adrenergic responsiveness. Fulvestrant and cross-sex hormone treatment (oestrogen or testosterone) vs. Vehicle was evaluated on β1- and β3-adrenoceptor mRNA expression and β-adrenergic vasorelaxation (p=<0.05). Oestrogen receptor inhibition with fulvestrant reduced vascular β1- and β3-adrenoceptor mRNA expression by approximately 50% and impaired β-adrenergic vasodilation in female rats.
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