Rat carotid artery responses to alpha-adrenergic receptor agonists and 5-HT after ovariectomy and hormone replacement.
OBJECTIVE
To compare the contractile responses to alpha-adrenergic receptor agonists and 5-HT in the rat carotid artery after ovariectomy and subsequent hormone replacement with 17beta-estradiol, progesterone, or the combination of 17beta-estradiol and progesterone.


BACKGROUND
The prevalence of migraine is higher in women than in men, and changes in 17beta-estradiol levels seem to affect the frequency of attacks in female migraineurs. However, the underlying mechanisms are not yet completely understood.


METHODS
After 1 week of acclimatization (Day 0), female Sprague-Dawley rats were either sham-operated or bilateral ovariectomized. One week later (Day 7), the ovariectomized rats were subcutaneously implanted with a pellet releasing over a 21-day period either placebo, 0.25 mg 17beta-estradiol, 50 mg progesterone, or the combination of the 2 hormones. Blood samples were collected on Days 0, 7, and 21 to measure plasma norepinephrine and epinephrine. On days 25 to 28, the animals were killed to isolate carotid artery and mount its segments in Mulvany myographs. Cumulative concentration response curves to alpha-adrenergic receptor agonists and 5-HT were constructed in the absence or presence of suitable antagonists.


RESULTS
The potency of norepinephrine in ovariectomized rats was significantly reduced in animals treated with progesterone as compared to those with placebo. In placebo-treated ovariectomized animals there was a noticeable response mediated by alpha2-adrenoceptors, in contrast to that in sham-operated or ovariectomized rats treated with 17beta-estradiol and progesterone, either alone or in combination. The plasma levels of norepinephrine and epinephrine were not significantly affected by either ovariectomy or the subsequent hormone replacement. The potency of 5-HT was significantly reduced in animals having circulating sex hormones as compared to that in placebo-treated ovariectomized animals.


CONCLUSIONS
Taken together, our results indicate that circulating progesterone and/or 17beta-estradiol may reduce the contraction of the rat carotid artery in response to norepinephrine and 5-HT. This effect of female sex hormones might be one of the factors through which these hormones aggravate migraine in women.
Mehrotra
Suneet
S
Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Gupta
Saurabh
S
Villalón
Carlos M
CM
Boomsma
Frans
F
Saxena
Pramod R
PR
MaassenVanDenbrink
Antoinette
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008881:Migraine Disorders / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
C094643:A 61603; D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D018490:Serotonin Agents; D013764:Tetrahydronaphthalenes; D010656:Phenylephrine; D012701:Serotonin; D011374:Progesterone; D004958:Estradiol; D011189:Potassium Chloride; D009638:Norepinephrine; D004837:Epinephrine