Characterization of the myocardial and renal renin–angiotensin system in normal cats and cats with hypertrophic cardiomyopathy

Figures

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  Figure 1. Angiotensin peptide metabolism, including Ang peptides AngI-IV, Ang1-7, and Ang1-5 and their catalysts. Abbreviations: ACE = angiotensin-converting enzyme; ACE2 = angiotensin-converting enzyme 2; Ang = angiotensin; AP = aminopeptidase; NEP = neprilysin; PEP = prolyl-endopeptidase.

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  Figure 2. Production rates of AngII and Ang1-7 were evaluated in tissue homogenates spiked with (A) AngI or (B) AngII and subjected to sequential additions of enzyme inhibitors. See text for details. Abbreviations: ACE = angiotensin-converting enzyme; ACE2 = angiotensin-converting enzyme 2; Ang = angiotensin; NEP = neprilysin; PCP = prolyl-carboxypeptidase; ZPP = z-pro-prolinal.

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  Figure 3. Formation rates ([pg/μg protein]/hour) of AngII in LVFW tissue incubated with AngI and formation rates of Ang1-7 in tissue incubated with either AngII or AngI in 5 normal cats (A, B, and C) and 5 cats with either stage B1 or C HCM (D, E, and F). (A and D) Homogenized LVFW tissue was incubated with AngI alone (control) and with the chymase inhibitor chymostatin or chymostatin plus the angiotensin-converting enzyme inhibitor lisinopril. (B and E) Homogenized tissue was incubated with AngII alone (control) and with the prolyl-carboxypeptidase and prolyl-endopeptidase inhibitor ZPP or ZPP with the angiotensin-converting enzyme 2 inhibitor MLN-4760. (C and F) Homogenized tissue was incubated with AngI and chymostatin and lisinopril (control) and with chymostatin, lisinopril, and the neprilysin inhibitor LBQ-657. Note: P values are adjusted for multiplicity; P values less than .01 are approximate. Abbreviations: Ang = angiotensin; HCM = hypertrophic cardiomyopathy; LVFW = left ventricular free wall; ZPP = z-pro-prolinal.

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  Figure 4. Formation rates ([pg/μg protein]/hour) of AngII in kidney tissue incubated with AngI (A) and formation rates of Ang1-7 in tissue incubated with either AngII (B) or AngI (C) in 5 normal cats and 2 cats with stage B1 HCM. (A) Homogenized LVFW tissue was incubated with AngI alone (control) and with the chymase inhibitor chymostatin or chymostatin plus the angiotensin-converting enzyme inhibitor lisinopril. (B) Homogenized tissue was incubated with AngII alone (control) and with the prolyl-carboxypeptidase and prolyl-endopeptidase inhibitor ZPP or ZPP with the angiotensin-converting enzyme 2 inhibitor MLN-4760. (C) Homogenized tissue was incubated with AngI and chymostatin and lisinopril (control) and with chymostatin, lisinopril, and the neprilysin inhibitor LBQ-657. Note: P values are adjusted for multiplicity; P values less than .01 are approximate. Abbreviations: Ang = angiotensin; HCM = hypertrophic cardiomyopathy; LVFW = left ventricular free wall; ZPP = z-pro-prolinal.

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  Figure 5. Overview of the experiments to evaluate relative contribution of renin–angiotensin system enzymes to the formation of either angiotensin II or angiotensin 1-7 in tissues collected postmortem. These relative enzyme contributions represent what was found in both the immediately frozen tissues and in the tissues where freezing was delayed for 3 h. Abbreviations: ACE = angiotensin-converting enzyme; ACE2 = angiotensin-converting enzyme 2; AP = angiotensin peptide; NEP = neprilysin; PCP = prolylcarboxypeptidase.