Angiotensin-(1-12) is an alternate substrate for angiotensin peptide production in the heart.
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.
Trask
Aaron J
AJ
Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. atrask@wfubmc.edu).
Jessup
Jewell A
JA
Chappell
Mark C
MC
Ferrario
Carlos M
CM
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism*; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System; D013997:Time Factors
D000809:Angiotensins; D010446:Peptide Fragments; C473112:Ren2 protein, mouse; C515557:proangiotensin-12, rat; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7)