Human renin-dependent hypertension in rats transgenic for human angiotensinogen

Hypertension
J BohlenderD Ganten

Abstract

To examine the utility of rats transgenic for human angiotensinogen in the study of human renin-induced hypertension, we first developed assays to measure both the human and rat renin-angiotensin systems in these rats. We used human and mouse renin, transgenic human angiotensinogen, and the human renin inhibitor Ro 42-5892 to determine human- and rat-specific plasma angiotensinogen concentrations, renin activity, and renin concentration. The assays were validated with rat and human plasma mixed in known amounts and with plasma from rats transgenic for human renin. We then tested the human angiotensinogen-transgenic rats by infusing recombinant human renin over 10 days (50 ng/h, n=4) with osmotic minipumps. High human angiotensinogen transgene expression was found in the liver, brain, kidney, gastrointestinal tract, and aorta, whereas rat angiotensinogen gene expression was detected in the liver and brain. During human renin infusion, blood pressure increased to >200/150 mm Hg. Before infusion, human angiotensinogen was 100-fold greater than rat angiotensinogen (141 +/- 73 versus 1.2 +/- 0.16 microg angiotensin l/mL); the relation was not changed by renin infusion. Plasma renin activity increased 300-fold; human plasma renin con...Continue Reading

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Citations

Sep 12, 2000·Current Hypertension Reports·X JeunemaitreP Corvol
Jan 20, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M TahmasebiG P Vinson
Oct 23, 2010·The Journal of Biological Chemistry·Marcus PohlFranziska Theilig
Jan 9, 2009·Journal of Cardiovascular Pharmacology·Ping XuThomas Walther
Jun 29, 2000·Annual Review of Biochemistry·D L Garbers, S K Dubois
Apr 1, 1999·Journal of Hypertension·J A StaessenR Fagard
Feb 22, 2011·Peptides·Ovidiu C BaltatuMichael Bader
Nov 1, 2008·Journal of the American Society of Hypertension : JASH·Luiza A RabeloNatalia Alenina
Dec 6, 2019·Frontiers in Cardiovascular Medicine·Carlos M FerrarioJasmina Varagic
Feb 14, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Carlos M FerrarioJasmina Varagic
Jun 5, 1998·The American Journal of Physiology·J BohlenderF C Luft
Oct 29, 2000·Journal of the American Society of Nephrology : JASN·Jürgen BohlenderFriedrich C Luft

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