[Correction added after online publication 2-Oct-2006: Order of author names has been modified and academic degrees of authors Gupta and Mehrotra have been updated]
Effects of Female Sex Hormones on Responses to CGRP, Acetylcholine, and 5-HT in Rat Isolated Arteries
Article first published online: 2 OCT 2006
Headache: The Journal of Head and Face Pain
Volume 47, Issue 4, pages 564–575, April 2007
How to Cite
Gupta, S., Mehrotra, S., Villalón, C., De Vries, R., Garrelds, I., Saxena, P. and VanDenBrink, A. M. (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: 564–575. doi: 10.1111/j.1526-4610.2006.00596.x
From the Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands (Drs. MaassenVanDenBrink, Gupta, De Vries, Garrelds, and Saxena); and Departamento De Farmacobiología, Cinvestav-Coapa, Tlalpan, México D.F., México (Dr. Villalón).
Drs. Gupta and Mehrotra contributed equally to this study.
- Issue published online: 2 OCT 2006
- Article first published online: 2 OCT 2006
- Accepted for publication August 10, 2006.
- calcitonin gene-related peptide;
- rat artery
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.