Details

Autor(en) / Beteiligte

• Haas, Erwin
• Lewis, LaVera
• Koshy, John T.
• Varde, Anita U.
• Renerts, Lea
• Bagai, Ramesh C.

Titel

Angiotensin II-Producing Enzyme III From Acidified Serum of Nephrectomized Dogs

Ist Teil von

• American journal of hypertension, 1989-09, Vol.2 (9), p.696-707

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

1989

Quelle

MEDLINE

Beschreibungen/Notizen

• A highly active angiotensin-producing enzyme (enzyme III) was obtained from the serum of bilaterally nephrectomized dogs b y acid treatment and ammonium sulfate fractionation. An inactive precursor (proenzyme III) was converted to enzyme III during prolonged storage (or by treatment with acid or with cathepsin G or by incubation at 38 ºC as described in the following paper). Enzyme III reacted maximally at pH 7.7 and it produced up to 400 ng of angiotensin II/mL serum/h (i.e., amounts 4000 times higher than that generated by the endogenous renin present in serum after bilateral nephrectomy). Enzyme III produced angiotensin II at identical rates when either dog angiotensinogen or angiotensin I was used as substrate, but the rate was 710 times higher with synthetic tetradecapeptide renin substrate. Enzyme III is not identical to renin, cathepsin G, tonin, enzyme I, enzyme II, the calcium-dependent angiotensin I-converting enzyme, or the calcium-independent carboxy peptidase, which acts b y sequential cleavage of angiotensin I. Enzyme III was inhibited by α-antitrypsin, diisopropyl fluorophosphate, and lima bean trypsin inhibitor (hence it is a serine proteinase). It was not inhibited b y Captopril, Teprotide, or Enalapril. It had been reported previously that cathepsin G released from neutrophil granulocytes, by producing high local concentrations of angiotensin II, may provide a mobile means for modulating blood flow in tissue microvasculature during the inflammatory response. The present study offers a new, additional pathway, by enzyme III, for a similar rapid formation of angiotensin II from serum protein substrate or angiotensin I. Am J Hypertens 1989; 2:696–707.