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| Slide Lecture Programs |
| 2000 Core Curriculum |
| The endothelium: New insights into the origins and treatment of CAD |
August 31, 2000
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| II: |
Interactions of the RAS: ACE and the angiotensin II and bradykinin pathways |
Slide 22 |
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ACE metabolizes Ang-(1-7) into Ang-(1-5): Effect with and without ACE inhibition
- This study demonstrated the role of ACE as the mechanism for the metabolism of Ang-(1-7).19
- In the first part of the study, which is not shown on the slide, lisinopril (alone or in combination with losartan) significantly increased the half-life of Ang-(1-7) in three strains of rats (normotensive, hypertensive, and transgenic) whereas the ARB losartan alone had no effect.
- An analysis of the metabolism of Ang-(1-7) in pulmonary membranes of untreated SHR rats, a tissue with a high peptidase activity, showed that Ang-(1-7) was degraded within 15 minutes. The primary metabolite resulting from the hydrolysis of Ang-(1-7) was identified as Ang-(1-5), an inactive peptide.
- As seen on the slide, the addition of the ACE inhibitor lisinopril to the membrane slowed the metabolism of Ang-(1-7) and abolished the formation of Ang-(1-5). Lisinopril increased the half-life of Ang-(1-7) approximately 15-fold (P < .01).
- A similar pattern of Ang-(1-7) metabolism was found in pulmonary membranes of the normotensive rats.
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