Primacy of angiotensin converting enzyme in angiotensin-(1-12) metabolism

Angiotensin-(1-12) [ANG-(1-12)], a new member of the renin-angiotensin system, is recognized as a renin independent precursor for ANG II. However, the processing of ANG-(1-12) in the circulation in vivo is not fully established. We examined the effect of angiotensin converting enzyme (ACE) and chyma...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2013-09, Vol.305 (5), p.H644-H650
Main Authors: Moniwa, Norihito, Varagic, Jasmina, Simington, Stephen W, Ahmad, Sarfaraz, Nagata, Sayaka, Voncannon, Jessica L, Ferrario, Carlos M
Format: Article
Language:English
Subjects:
ACE inhibitors
Angiotensin I - metabolism
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Angiotensinogen - administration & dosage
Angiotensinogen - metabolism
Angiotensinogen - pharmacology
Animals
Blood Pressure - drug effects
Call for Papers
Chymases - antagonists & inhibitors
Chymases - drug effects
Chymases - metabolism
Disease Models, Animal
Hypertension - metabolism
Hypertension - physiopathology
Infusions, Intravenous
Lisinopril - pharmacology
Male
Medical treatment
Oligopeptides - pharmacology
Peptide Fragments - administration & dosage
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Peptides
Peptidyl-Dipeptidase A - drug effects
Peptidyl-Dipeptidase A - metabolism
Plasma
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Rodents
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Summary:Angiotensin-(1-12) [ANG-(1-12)], a new member of the renin-angiotensin system, is recognized as a renin independent precursor for ANG II. However, the processing of ANG-(1-12) in the circulation in vivo is not fully established. We examined the effect of angiotensin converting enzyme (ACE) and chymase inhibition on angiotensin peptides formation during an intravenous infusion of ANG-(1-12) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR were assigned to a short ANG-(1-12) infusion lasting 5, 15, 30, or 60 min (n = 4-10 each group). In another experiment WKY and SHR were assigned to a continuous 15-min ANG-(1-12) infusion with pretreatment of saline, lisinopril (10 mg/kg), or chymostatin (10 mg/kg) (n = 7-13 each group). Saline or lisinopril were infused intravenously 15 min before the administration of ANG-(1-12) (2 nmol·kg(-1)·min(-1)), whereas chymostatin was given by bolus intraperitoneal injection 30 min before ANG-(1-12). Infusion of ANG-(1-12) increased arterial pressure and plasma ANG-(1-12), ANG I, ANG II, and ANG-(1-7) levels in WKY and SHR. Pretreatment with lisinopril caused increase in ANG-(1-12) and ANG I and large decreases in ANG II compared with the other two groups in both strains. Pretreatment of chymostatin had no effect on ANG-(1-12), ANG I, and ANG II levels in both strains, whereas it increased ANG-(1-7) levels in WKY. We conclude that ACE acts as the primary enzyme for the conversion of ANG-(1-12) to smaller angiotensin peptides in the circulation of WKY and SHR and that chymase may be an ANG-(1-7) degrading enzyme.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00210.2013