In situ production of angiotensin II by fibrosed rat pericardium

Ou Ruchong, Yao Sun, Venkataseshu K. Ganjam, Karl Weber

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Following pericardiotomy in rats, subsequent fibrosis of the visceral pericardium becomes a site of high-density angiotensin-converting enzyme (ACE) binding. This study was undertaken to determine whether this exteriorized site of ACE activity is associated with angiotensin II (AngII) production. Four weeks after pericardiotomy, hearts were isolated and maintained by Krebs-Henseleit perfusion; coronary venous and Thebesian drainage were removed by cannulae. Following a 30-min period of stabilization, a balloon containing superfusate was placed around the heart. Superfusate composition was controlled and included either lisinopril (10-7 mol/l), angiotensin I (AngI, 10-7 mol/l), or angiotensinogen (10-6 mol/l). Sixty min later, superfusate AngII concentration was determined (high-performance liquid chromatography followed by radioimmunoassay). Pericardial fibrosis was confirmed by picrosirius red staining and its high-density ACE binding by quantitative in vitro autoradiography (125I-351A). ACE activity was measured by hippuryl-histidyl-leucine degradation. In coronary effluent, AngII concentration and ACE activity were not different between controls and hearts with pericardial fibrosis. Compared to unoperated, age/sex-matched control hearts, however, we found those with pericardial fibrosis to have: (a) significantly (P < 0.05) greater tissue ACE activity (118.42 ± 6.66 v 89.45 ± 7.70 nmol/min/g); (b) significantly (P < 0.01) greater superfusate AngII concentration (4.98 ± 0.94 v 1.43 ± 0.28 pg/ml); (c) lisinopril markedly attenuated superfusate AngII concentration to that seen in controls; (d) exogenous AngI markedly increased AngII production (13.76 ± 1.65 v 4.98 ± 0.94 pg/ml); and (e) exogenous angiotensinogen did not alter superfusate AngII. Thus, high-density ACE binding and ACE activity of fibrosed pericardium is responsible for AngII production in this in vitro model. Cells involved in generating AngI at this site are uncertain and may involve fibroblast-like cells that express ACE and have ACE activity. The role of local AngII production is unknown, but its autocrine/paracrine properties may regulate collagen turnover of these cells.

Original languageEnglish (US)
Pages (from-to)1319-1327
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number6
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Pericardium
Peptidyl-Dipeptidase A
Angiotensin II
Fibrosis
Pericardiectomy
Lisinopril
Angiotensinogen
Angiotensin I
Autoradiography
Radioimmunoassay
Drainage
Collagen
Perfusion
Fibroblasts
High Pressure Liquid Chromatography
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

In situ production of angiotensin II by fibrosed rat pericardium. / Ruchong, Ou; Sun, Yao; Ganjam, Venkataseshu K.; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 28, No. 6, 01.01.1996, p. 1319-1327.

Research output: Contribution to journalArticle

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