Paradoxical regulation of short promoter human renin transgene by angiotensin ii. Hypertension 2001 Feb;37(2 Pt 2):403-7
Date
03/07/2001Pubmed ID
11230308DOI
10.1161/01.hyp.37.2.403Scopus ID
2-s2.0-0035090179 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
We previously reported the generation of transgenic mice containing the entire human renin gene with a 900-bp promoter. To determine whether all the required elements for angiotensin II-mediated suppression of human renin are present in these mice, angiotensin II was chronically infused by means of osmotic minipump at both low and high doses, 200 and 1000 ng/kg per minute, respectively. Blood pressure was measured by tail-cuff, and kidney renin mRNA levels were quantitated using ribonuclease protection assays. Blood pressure was unchanged in mice receiving either vehicle or low-dose angiotensin II infusion but was increased by approximately 40 mm Hg with the higher dose of angiotensin II. Mouse renin mRNA decreased by >60% during both pressor and nonpressor angiotensin II infusion. Human renin mRNA was not suppressed by nonpressor angiotensin II and was paradoxically increased 1.9-fold by pressor angiotensin II. The lack of upregulation during nonpressor angiotensin II suggested that the increase might be pressure-mediated. To test this, the angiotensin II-induced increase in blood pressure was prevented by coadministration of the vasodilator, hydralazine (15 mg/kg per day). Hydralazine alone decreased blood pressure (-27+/-3 mm Hg) and increased mouse renin mRNA 2.4-fold. Human renin mRNA was unresponsive to this vasodilator-induced fall in pressure and despite the normalization of blood pressure by hydralazine, high-dose angiotensin II still caused a 2.1-fold increase in human renin mRNA. Thus, the first 900 bp of the human renin promoter does not contain all the elements required for appropriate angiotensin II-mediated suppression of human renin mRNA.
Author List
Keen HL, Sigmund CDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAngiotensinogen
Animals
Blood Pressure
Dose-Response Relationship, Drug
Gene Expression Regulation
Humans
Hydralazine
Infusion Pumps, Implantable
Kidney
Mice
Mice, Transgenic
Promoter Regions, Genetic
RNA, Messenger
Renin
Up-Regulation
Vasodilator Agents