Central vasopressor responses to conjugated estrogens in rats may be mediated via a renin-angiotensin system in the brain.
Central effects of sex steroids on cardiovascular regulation and on behavior were investigated by injecting conjugated estrogens i.c.v. in conscious or anesthetized rats. Conjugated estrogens (0.1-10 micrograms) produced dose-related increases in pressure and behavioral excitation in all rats and drinking in some rats. Marked increases ii pressure and excitation with tonic convulsions resulting in death were produced by similar injections of conjugated estrogens (100 micrograms). Pretreatment with angiotensin I converting enzyme inhibitor or angiotensin II analog abolished both vasopressor responses and behavioral excitation in conscious rats. When rats were later anesthetized with urethane to allow recording of sympathetic nerve activity, 10 and 100 micrograms of conjugated estrogens produced dose-related vasopressor responses accompanied by corresponding increases in peripheral sympathetic nerve activity. Again, converting enzyme inhibitor or angiotensin II analog abolished the increases in both blood pressure and sympathetic nerve activity. By contrast, when conjugated estrogens were injected i.v. up to 2 mg/kg, neither blood pressure nor sympathetic outflow was affected. Collectively, our results suggest that conjugated estrogens infused centrally activate a renin-angiotensin system in the brain, which results in sympathetic hyperactivity leading to blood pressure elevation.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D004966:Estrogens, Conjugated (USP)