Key Points
- To determine whether non-ACE enzymes contribute to cardiac angiotensin I-to-II conversion and establish the endothelial versus extra-endothelial localization of converting enzymes in intact rat hearts.
- Perfused isolated rat Langendorff hearts with angiotensin I (5–10 pmol/ml) to separately collect coronary effluent and interstitial fluid.
- Tested hearts under control conditions, with the ACE inhibitor captopril (1 µmol/l), and following endothelial stripping via 0.2% Triton X-100.
- Quantified angiotensin I and II concentrations in effluent and interstitial fluid via radioimmunoassay.
- In control hearts, 45% of arterial angiotensin I was extracted during coronary passage, with interstitial angiotensin I concentrations 3- to 4-fold lower than coronary effluent while angiotensin II levels were similar.
- Captopril and endothelial removal did not change coronary angiotensin I extraction but increased interstitial angiotensin I levels 2-fold and 3-fold, respectively.
- Captopril reduced the angiotensin II/I ratio by 83% in coronary effluent and 93% in interstitial fluid, whereas endothelial removal reduced the ratios by 33% and 71%.
Structured PICO
PPopulationIsolated perfused rat hearts (Langendorff preparation)
IInterventionPerfusion with angiotensin I (5-10 pmol/ml) in the presence of captopril (1 micromol/l) or after endothelium removal with 0.2% triton X-100
CComparatorPerfusion with angiotensin I under control conditions
OOutcomeAngiotensin I and angiotensin II concentrations in coronary effluent and interstitial fluidsurrogate
In the intact rat heart, ACE is the primary enzyme responsible for converting angiotensin I to angiotensin II in both the coronary vascular bed and the interstitium, challenging recent findings from homogenized hearts that suggested chymase was the main contributor.