Modulation of tissue angiotensinogen gene expression by glucocorticoids, estrogens, and androgens in SHR and WKY rats.
Local or tissue renin angiotensin systems are thought to participate in cardiovascular regulation. However, little information is available on the mechanisms by which renin and angiotensinogen synthesis and secretion are regulated in these tissues. In view of the importance of steroid hormones in the regulation of hepatic angiotensinogen, we have examined the effects of dexamethasone, ethinyl estradiol, or dihydrotestosterone on angiotensinogen gene expression in peripheral or cerebral tissues of Wistar Kyoto (WKY) or spontaneously hypertensive rats (SHR). Following a single injection of dexamethasone (7 mg/kg) the concentrations of angiotensinogen mRNA increased in nearly all organs examined. The differences to controls were higher in SHR than in WKY. Dexamethasone in low doses (10 micrograms/kg/day) given for 10 days did not alter angiotensinogen mRNA or blood pressure in control animals, but increased both parameters in the hypertensive strain. The response to a single dose of ethinyl estradiol (3 mg/kg) was not as uniform as that to dexamethasone, and a tendency for a higher sensitivity was found in SHR. High stimulation rates were found in liver and kidneys of both strains. A single dose of dihydrotestosterone (10 mg/kg) did not significantly affect angiotensinogen mRNA in any organ. Only when a high dose of 50 mg/kg was given daily for 20 days, was angiotensinogen mRNA increased in some tissues. These data indicate that glucocorticoids and estrogens participate in the regulation of angiotensinogen gene expression in several extrahepatic tissues. The higher sensitivity to glucocorticoids in SHR may be relevant for the development of hypertension in this strain.
Department of Pharmacology, University of Heidelberg, Germany.
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Klett
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Hellmann
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Hackenthal
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Ganten
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004351:Drug Resistance; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D013256:Steroids / Q000494:pharmacology*; D014018:Tissue Distribution
D012333:RNA, Messenger; D013256:Steroids; D013196:Dihydrotestosterone; D000808:Angiotensinogen; D004997:Ethinyl Estradiol; D003907:Dexamethasone