Bradykinin receptor and tissue ACE binding in myocardial fibrosis

Response to chronic angiotensin II or aldosterone administration in rats

Yao Sun, Anna Ratajska, Karl Weber

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Y. Sun, A. Ratajska and K. T. Weber. Bradykinin Receptor and Tissue ACE Binding in Myocardial Fibrosis: Response to Chronic Angiotensin II or Aldosterone Administration in Rats. Journal of Molecular and Cellular Cardiology (1995) 27, 813-822. High density angiotensin converting enzyme (ACE) binding is present in the perivascular fibrosis involving intramyocardial coronary arteries and the microscopic scarring of the myocardium that accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought to determine whether bradykinin (BK) receptor binding was associated with ACE binding in each of these experimental models. BK receptor binding was localized and quantified by in vitro quantitative autoradiography, using [125I-Tyr8]BK. In serial sections of the same heart hematoxylin and eosin (H&E) and picrosirius red (PSR) staining were utilized to address cardiac myocyte injury and fibrosis respectively. Four experimental groups were examined: unoperated, untreated, age/sex matched controls; age/sex matched uninephrectomized control rats receiving a high sodium diet; animals that received AngII (9 μg/h sc) for 2, 4 or 6 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/h sc) for similar periods of time. We found: (a) myocardial fibrosis, including perivascular fibrosis and microscopic scarring, at week 2 of AngII, but not until week 4 or more of ALDO treatment; (b) low BK receptor binding in normal ventricles that was increased in scars and markedly increased in perivascular fibrosis at week 2 of AngII and each increased further at week 4 and 6 of AngII; (c) low BK receptor binding at week 2 and 4 weeks of ALDO treatment which became markedly increased at fibrous tissue sites at week 6. BK receptor and ACE binding were anatomically coincident and localized to each site of fibrosis in both models. The co-location of BK receptor and ACE binding in these models raises the prospect that fibrous tissue ACE may utilize BK as substrate and BK, in turn, may play a role in fibrous tissue formation.

Original languageEnglish (US)
Pages (from-to)813-822
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Bradykinin Receptors
Peptidyl-Dipeptidase A
Aldosterone
Angiotensin II
Fibrosis
Bradykinin
Cicatrix
Sodium
Diet
Hematoxylin
Eosine Yellowish-(YS)
Cardiology
Autoradiography
Cardiac Myocytes
Coronary Vessels
Myocardium
Theoretical Models
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Bradykinin receptor and tissue ACE binding in myocardial fibrosis: Response to chronic angiotensin II or aldosterone administration in rats",
abstract = "Y. Sun, A. Ratajska and K. T. Weber. Bradykinin Receptor and Tissue ACE Binding in Myocardial Fibrosis: Response to Chronic Angiotensin II or Aldosterone Administration in Rats. Journal of Molecular and Cellular Cardiology (1995) 27, 813-822. High density angiotensin converting enzyme (ACE) binding is present in the perivascular fibrosis involving intramyocardial coronary arteries and the microscopic scarring of the myocardium that accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought to determine whether bradykinin (BK) receptor binding was associated with ACE binding in each of these experimental models. BK receptor binding was localized and quantified by in vitro quantitative autoradiography, using [125I-Tyr8]BK. In serial sections of the same heart hematoxylin and eosin (H&E) and picrosirius red (PSR) staining were utilized to address cardiac myocyte injury and fibrosis respectively. Four experimental groups were examined: unoperated, untreated, age/sex matched controls; age/sex matched uninephrectomized control rats receiving a high sodium diet; animals that received AngII (9 μg/h sc) for 2, 4 or 6 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/h sc) for similar periods of time. We found: (a) myocardial fibrosis, including perivascular fibrosis and microscopic scarring, at week 2 of AngII, but not until week 4 or more of ALDO treatment; (b) low BK receptor binding in normal ventricles that was increased in scars and markedly increased in perivascular fibrosis at week 2 of AngII and each increased further at week 4 and 6 of AngII; (c) low BK receptor binding at week 2 and 4 weeks of ALDO treatment which became markedly increased at fibrous tissue sites at week 6. BK receptor and ACE binding were anatomically coincident and localized to each site of fibrosis in both models. The co-location of BK receptor and ACE binding in these models raises the prospect that fibrous tissue ACE may utilize BK as substrate and BK, in turn, may play a role in fibrous tissue formation.",
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N2 - Y. Sun, A. Ratajska and K. T. Weber. Bradykinin Receptor and Tissue ACE Binding in Myocardial Fibrosis: Response to Chronic Angiotensin II or Aldosterone Administration in Rats. Journal of Molecular and Cellular Cardiology (1995) 27, 813-822. High density angiotensin converting enzyme (ACE) binding is present in the perivascular fibrosis involving intramyocardial coronary arteries and the microscopic scarring of the myocardium that accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought to determine whether bradykinin (BK) receptor binding was associated with ACE binding in each of these experimental models. BK receptor binding was localized and quantified by in vitro quantitative autoradiography, using [125I-Tyr8]BK. In serial sections of the same heart hematoxylin and eosin (H&E) and picrosirius red (PSR) staining were utilized to address cardiac myocyte injury and fibrosis respectively. Four experimental groups were examined: unoperated, untreated, age/sex matched controls; age/sex matched uninephrectomized control rats receiving a high sodium diet; animals that received AngII (9 μg/h sc) for 2, 4 or 6 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/h sc) for similar periods of time. We found: (a) myocardial fibrosis, including perivascular fibrosis and microscopic scarring, at week 2 of AngII, but not until week 4 or more of ALDO treatment; (b) low BK receptor binding in normal ventricles that was increased in scars and markedly increased in perivascular fibrosis at week 2 of AngII and each increased further at week 4 and 6 of AngII; (c) low BK receptor binding at week 2 and 4 weeks of ALDO treatment which became markedly increased at fibrous tissue sites at week 6. BK receptor and ACE binding were anatomically coincident and localized to each site of fibrosis in both models. The co-location of BK receptor and ACE binding in these models raises the prospect that fibrous tissue ACE may utilize BK as substrate and BK, in turn, may play a role in fibrous tissue formation.

AB - Y. Sun, A. Ratajska and K. T. Weber. Bradykinin Receptor and Tissue ACE Binding in Myocardial Fibrosis: Response to Chronic Angiotensin II or Aldosterone Administration in Rats. Journal of Molecular and Cellular Cardiology (1995) 27, 813-822. High density angiotensin converting enzyme (ACE) binding is present in the perivascular fibrosis involving intramyocardial coronary arteries and the microscopic scarring of the myocardium that accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO). As a kininase II, ACE degrades bradykinin. Herein we sought to determine whether bradykinin (BK) receptor binding was associated with ACE binding in each of these experimental models. BK receptor binding was localized and quantified by in vitro quantitative autoradiography, using [125I-Tyr8]BK. In serial sections of the same heart hematoxylin and eosin (H&E) and picrosirius red (PSR) staining were utilized to address cardiac myocyte injury and fibrosis respectively. Four experimental groups were examined: unoperated, untreated, age/sex matched controls; age/sex matched uninephrectomized control rats receiving a high sodium diet; animals that received AngII (9 μg/h sc) for 2, 4 or 6 weeks; and uninephrectomized rats on a high sodium diet that received ALDO (0.75 μg/h sc) for similar periods of time. We found: (a) myocardial fibrosis, including perivascular fibrosis and microscopic scarring, at week 2 of AngII, but not until week 4 or more of ALDO treatment; (b) low BK receptor binding in normal ventricles that was increased in scars and markedly increased in perivascular fibrosis at week 2 of AngII and each increased further at week 4 and 6 of AngII; (c) low BK receptor binding at week 2 and 4 weeks of ALDO treatment which became markedly increased at fibrous tissue sites at week 6. BK receptor and ACE binding were anatomically coincident and localized to each site of fibrosis in both models. The co-location of BK receptor and ACE binding in these models raises the prospect that fibrous tissue ACE may utilize BK as substrate and BK, in turn, may play a role in fibrous tissue formation.

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