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Am J Physiol Heart Circ Physiol 294: H2242-H2247, 2008. First published March 21, 2008; doi:10.1152/ajpheart.00175.2008
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Angiotensin-(1-12) is an alternate substrate for angiotensin peptide production in the heart

Aaron J. Trask, Jewell A. Jessup, Mark C. Chappell, and Carlos M. Ferrario

Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Submitted 17 February 2008 ; accepted in final form 13 March 2008

Identification of angiotensin-(1-12) as an intermediate precursor derived directly from angiotensinogen led us to explore whether the heart has the capacity to process angiotensin-(1-12) into biologically active angiotensin peptides. The generation of angiotensin I, angiotensin II, and angiotensin-(1-7) from exogenous angiotensin-(1-12) was evaluated in the effluent of isolated perfused hearts mounted on a Langendorff apparatus in three normotensive and two hypertensive strains: Sprague-Dawley, Lewis, congenic mRen2.Lewis, Wistar-Kyoto, and spontaneously hypertensive rats. Hearts were perfused with Krebs solution for 60 min before and after the addition of angiotensin-(1-12) (10 nmol/l). Angiotensin-(1-12) caused the rapid appearance of both angiotensin I and angiotensin II in the perfusate that peaked between 30 and 60 min of recirculation. Production of angiotensin-(1-7) from exogenous angiotensin-(1-12) rose steadily over the course of the 60-min experiment. These data directly demonstrate that angiotensin-(1-12) is a substrate for the formation of angiotensin peptides in cardiac tissue. This finding further suggests that this angiotensinogen-derived product is a previously unrecognized important precursor peptide to the renin-angiotensin system cascade.

angiotensinogen; angiotensin II; angiotensin-(1-7); renin; hypertension


Address for reprint requests and other correspondence: A. J. Trask, Hypertension and Vascular Research Center, Dept. of Physiology and Pharmacology, Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157 (e-mail: atrask{at}wfubmc.edu)




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