Effect of levonorgestrel and ethinyloestradiol on vasoconstriction in rat isolated vasculature.
Female Sprague-Dawley rats were injected s.c. with 0.2 micrograms day-1 ethinyloestradiol (EE2) or 2.0 micrograms day-1 levonorgestrel (NG), procedures previously shown to increase systolic blood pressure. Increases in perfusion pressure to clonidine, phenylephrine, noradrenaline (NA) and angiotensin II (AII) were observed in rat isolated tail arteries, and to NA in the isolated mesenteric vasculature from steroid and vehicle-treated rats. NG treatment for four weeks produced increases in sensitivity to phenylephrine and NA in rat tail arteries; at 6 weeks the increases in sensitivity had largely disappeared but the maximum responses to clonidine and phenylephrine were increased. No change in sensitivity to AII was observed with NG. In contrast, EE2 treatment for six weeks produced increases in sensitivity to AII, and a decrease in sensitivity and maximum response to clonidine but not to phenylephrine or NA, in tail arteries. Responses to NA in the mesenteric vasculature were increased after 6 weeks NG treatment but unaffected after 12 weeks EE2 treatment. It is concluded that NG treatment stimulates alpha-adrenoceptor number, affinity or receptor-linked Ca2+ events which may contribute to its previously demonstrated hypertensive effect. The increased responsiveness to AII but not the decrease in alpha 2-adrenoceptor responsiveness may be associated with the chronic hypertension induced by EE2.
Byrne
K B
KB
Division of Biological and Health Sciences, Deakin University Victoria, Australia.
Stanton
B J
BJ
Coupar
I M
IM
Burcher
E
E
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D016912:Levonorgestrel; D009638:Norepinephrine / Q000494:pharmacology; D009644:Norgestrel / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D003271:Contraceptive Agents, Female; D000804:Angiotensin II; D010656:Phenylephrine; D009644:Norgestrel; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D003000:Clonidine; D009638:Norepinephrine