Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in rat isolated arteries.
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, 17beta-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 17beta-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 17beta-estradiol as compared to the placebo-treated rats. Acetylcholine-induced relaxations were potentiated in the caudal artery from rats treated with the combination of 17beta-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.


CONCLUSIONS
Our results show that 17beta-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.
Gupta
Saurabh
S
Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
Mehrotra
Suneet
S
Villalón
Carlos
C
De Vries
René
R
Garrelds
Ingrid
I
Saxena
Pramod
P
Vandenbrink
Antoinette Maassen
AM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D012739:Gonadal Steroid Hormones / Q000145:classification / Q000494:pharmacology*; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D012739:Gonadal Steroid Hormones; D012701:Serotonin; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine