This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Milsted, A. Articles by Ferrario, C. M. Search for Related Content PubMed PubMed Citation Articles by Milsted, A. Articles by Ferrario, C. M.

(Hypertension. 1996;28:678-681.)
© 1996 American Heart Association, Inc.

Articles

Differential Regulation of Angiotensinogen Transcripts After Renin Infusion

Amy Milsted; Masato Nishimura; K. Bridget Brosnihan; Carlos M. Ferrario

the Department of Brain and Vascular Research, The Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Amy Milsted, PhD, Department of Biology, The University of Akron, Akron, OH 44325-3908. E-mail amymilsted@uakron.edu.

To investigate angiotensinogen regulation in high-renin hypertension, we infused porcine renin intravenously at either a low (4 mU/kg per hour, n=6) or high (20 mU/kg per hour, n=9) dose into male Sprague-Dawley rats (225 to 250 g) for 5 days using osmotic minipumps. Control rats received 0.9% NaCl. In renin-infused rats, mean arterial pressure and plasma renin activity were significantly elevated. Both low- and high-renin infusions lowered plasma angiotensinogen levels. Plasma angiotensin II was elevated in rats given renin but reached statistical significance only at the higher dose. Angiotensinogen mRNA isolated from the liver, adrenal gland, kidney, and brain was measured by slot blot analysis. Both renin doses were associated with significant decreases in the levels of liver and hypothalamic angiotensinogen mRNA. In the medulla oblongata, angiotensinogen mRNA was reduced only by the higher renin dose. The lower dose increased angiotensinogen mRNA in the adrenal gland, and in kidney, angiotensinogen mRNA level was unchanged by renin infusion. Angiotensinogen mRNA visualized on Northern blots showed that the number of mRNA species in liver decreased from three in control rats to a single mRNA species after renin infusion. Tissue differences in the size of the major angiotensinogen mRNA species were also apparent. This, together with changes in the total hybridization signal of angiotensinogen mRNA in tissues, suggests that renin differentially affects the different angiotensinogen mRNA transcripts. Results of this study indicate that angiotensinogen gene expression is regulated not only by alterations in levels of circulating angiotensin II but also by other mechanisms, presently unidentified, that are activated by renin infusions.

Key Words: gene expression • renin-angiotensin system • angiotensin II