Expression and function of angiotensin converting enzyme, chymase, and angiotensin II in the human radial artery and internal thoracic artery Julie A.A.

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Presentation transcript:

Expression and function of angiotensin converting enzyme, chymase, and angiotensin II in the human radial artery and internal thoracic artery Julie A.A Borland, BSc, Adrian H Chester, PhD, Serena J Rooker, PhD, John Wharton, PhD, Neil Davie, BSc, Mohamed Amrani, MD, PhD, Magdi H Yacoub The Annals of Thoracic Surgery Volume 70, Issue 6, Pages 2054-2063 (December 2000) DOI: 10.1016/S0003-4975(00)01855-5

Fig 1 The contractile response of human radial artery (squares) and internal thoracic artery (circles) vessel segments to increasing concentrations of (A) angiotensin I (10−10 to 10−6 mol/L) and (B) angiotensin II (10−10 to 10−6 mol/L). Values are expressed as the mean of the absolute contractile response (mN) ± standard error of the mean. ∗p < 0.05 for radial artery compared to internal thoracic artery. The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)

Fig 2 The contractile effect of angiotensin II (10−10 to 10−6 mol/L) in the radial artery, in the presence of either vehicle (squares), the AT1-receptor antagonist losartan (1 μmol/L) (circles), or the AT2-receptor antagonist PD123319 (1 μmol/L) (triangles). Contractions are expressed as the mean percentage of the response to 90 mmol/L potassium chloride ± standard error of the mean. ∗p < 0.05 for control versus losartan. The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)

Fig 3 The contractile response of angiotensin I (10−10 to 10−6 mol/L) in (A) the radial artery and (B) the internal thoracic artery, in the presence of either vehicle (squares), the ACE inhibitor quinaprilat (1 μmol/L) (circles), the chymase inhibitor chymostatin (10 μmol/L) (triangles), or both quinaprilat (1 μmol/L) and chymostatin (10 μmol/L) combined (diamonds). Contractions are expressed as the mean percentage of the response to 90 mmol/L potassium chloride ± standard error of the mean. The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)

Fig 4 A representative example of transverse sections of human radial artery illustrating [125I]-(Sarcosine1-Isoleucine8) angiotensin II (2.5 nmol/L) binding in (A) the absence (total) of unlabelled (Sarcosine1-Isoleucine8) angiotensin II and (B) the presence of unlabelled peptide (2.5 nmol/L) (nonspecific binding), as well as (C) in the presence of the AT1-selective competitor losartan (1 μmol/L), and (D) in the presence of the AT2-selective competitor PD123319 (1 μmol/L). Scale bar = 2 mm. Panel (E) is a cross section of the same radial artery stained with Mayer’s hematoxylin and eosin, scale bar = 0.4 mm. (L = the blood vessel lumen; M = medial layer.) The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)

Fig 5 Reverse transcription–polymerase chain reaction amplification of angiotensin converting enzyme and chymase from cDNA prepared from a representative example of (A) radial artery and (B) internal thoracic artery. Lanes 1 and 2 show polymerase chain reaction negative controls for angiotensin converting enzyme and chymase, respectively. Lane 3 shows the amplification products for angiotensin converting enzyme with positive control cDNA prepared from human tricuspid valve endothelial cells. Lane 4 shows the amplification products for chymase with positive control cDNA prepared from human left ventricle. Lanes 5 and 6 are the amplified products for angiotensin converting enzyme 615 base pairs (bp) and chymase 651 bp, respectively (upper gels). All vessel segments amplified the housekeeping gene β-actin (lower gels). Markers (M) were enhanced 100 bp DNA ladder. The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)

Fig 6 Transverse sections of representative examples of human radial artery (panels A, C, E, and G) and internal thoracic artery (panels B, D, F, and H), stained with an immunohistochemical technique, showing positive staining (dark gray and black) (filled black arrows) for angiotensin II (ANG II) localized to the medial layer of the blood vessels (A and B), positive staining for angiotensin converting enzyme (ACE) localized to the luminal endothelial cells and those lining the vasa vasorum (C and D) (filled black arrows), as well as paler staining in the smooth muscle layer. Panels E and F demonstrate positive staining for chymase in the granules contained within the mast cells as well as those released into the adventitia (filled black arrows). No staining was observed in control sections (G and H). The scale bar = 0.2 mm. (L = lumen; M = medium; A = ventitia.) The Annals of Thoracic Surgery 2000 70, 2054-2063DOI: (10.1016/S0003-4975(00)01855-5)