Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB327

Poster Communications

Estrogen determines the sex-differences in adrenergic vessel tone regulation

I. Kopaliani1, K. Riedel1, B. Zatschler1, C. Friebel1, B. Müller1, A. Deussen1

1. Institute of Physiology, Technische Universität Dresden, Dresden, Germany.

Vessels of female rats react with stronger vasorelaxation and weaker vasoconstriction to adrenergic stimulation than vessels of males. Although we have previously shown that these sex-specific differences rely on endothelial β-adrenoceptors, the role of sex-hormones in endothelial β-adrenoceptor expression and related vessel tone regulation is unknown. Here we investigated the role of female and male sex-hormones on β-adrenoceptor expression and adrenergic vessel tone regulation. Five weeks old female and male Wistar rats were ovariectomized and orchiectomized, respectively, under anesthesia with 3% isoflurane and analgesia with 1 mg/kg Carprofen at the age of 5-weeks. As controls, a sham-operated, a hormone substituted (2 mg/kg, twice a week) and a vehicle group of rats were examined. At the age of 12-weeks, the rats were sacrificed with a Ketamine overdose (90 mg/kg plus 10 mg/kg Xylazine). Vasoconstriction (norepinephrine) and vasorelaxation (isoprenaline and β3-agonist BRL) of isolated aortas were assessed with Mulvany myograph. Additionally, a qRT-PCR for quantification of β-adrenoceptor mRNA levels in aorta was performed. The sex-specific differences in vasoconstriction and relaxation in rat aorta was eliminated after ovariectomy in female rats. Compared to sham operated females, ovariectomy increased aortic vasoconstriction in response to norepinephrine more than 2-fold. Vasorelaxation by isoprenaline and a β3-agonist was significantly (P<0.01) reduced after ovariectomy. Compared to vehicle, estrogen substitution largely (P<0.05) restored sex-specific differences in vasoconstriction and vasorelaxation in ovariectomized rats. Differences in vasoconstriction and vasorelaxation between sexes were profoundly diminished in presence of selective β1- and β3-adrenoceptor antagonists and L-NMMA which blocks eNOS. mRNA levels of β1- and β3, but not β2- adrenoreceptors were significantly (P<0.05) higher in aortas of sham operated females than in aortas of sham operated males. Ovariectomy abolished this difference by decreasing β1- and β3- adrenoreceptor expression in female rats, without affecting the expression of β2-adrenoreceptors. Consistently, estrogen substitution in ovariectomized female rats almost completely (P<0.05) restored β1- and β3-adrenoreceptor expression. Orchiectomy or testosterone treatment did not affect aortic vasoconstriction and vasorelaxation nor ß-adrenoceptor expression in aortas of male rats. In conclusion, the sex-specific differences in vasoconstriction and vasorelaxation in rat aorta are estrogen, but not testosterone-dependent. Estrogen determines these differences via regulation of vascular endothelial β1- and β3-adrenoreceptor expression.

Where applicable, experiments conform with Society ethical requirements