Background. - Female sex hormones are implicated in the modulation of reactivity of a wide range of blood vessels under physiological as well as pathological conditions. Migraine, a neurovascular syndrome, is 3 times more prevalent in women during their reproductive period than in men. Objective. - This study sets out to investigate the effects of the female sex steroids, 17β-estradiol and progesterone (separately and in combination) on vasoactive responses to calcitonin gene-related peptide (CGRP), acetylcholine, and 5-hydroxytryptamine (5-HT) in rat isolated mesenteric, caudal, and basilar arteries. Methods. - Female Sprague-Dawley rats were ovariectomized (Day 0) and 7 days later subcutaneously implanted with pellets releasing over a 21-day period 17β-estradiol (0.25 mg), progesterone (50 mg), their combination, or placebo. On days 25-28, the animals were killed, arteries isolated and mounted in Mulvany myographs, and cumulative concentration response curves to CGRP, acetylcholine, and 5-HT were constructed. Results. - The relaxant responses to CGRP were significantly potentiated in mesenteric and caudal arteries from rats treated with 17β-estradiol as compared to the placebo-treated rats. Acetylcholine-induced relaxations were potentiated in the caudal artery from rats treated with the combination of 17β-estradiol and progesterone, as compared to that from placebo-treated rats. The 5-HT-induced contractions in the 3 arteries were not significantly different in efficacy or potency. Conclusion. - Our results show that 17β-estradiol potentiates CGRP-induced relaxations in the mesenteric and caudal arteries, while the combination treatment enhances acetylcholine-induced relaxations in the caudal artery. Although these in vitro experiments have been carried out in rats and a direct extrapolation to migraine in humans is not possible, our results may provide a new avenue to study the effects of sex steroids on vascular reactivity.

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Headache: the journal of head and face pain
Erasmus MC: University Medical Center Rotterdam

Gupta, S., Mehrotra, S., Villalón, C., de Vries, R., Garrelds, I., Saxena, P. R., & Maassen van den Brink, A. (2007). Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in rat isolated arteries. Headache: the journal of head and face pain, 47(4), 564–575. doi:10.1111/j.1526-4610.2006.00596.x