In isolated rabbit thoracic aorta, luminal angiotensin I was partially converted to angiotensin II (14% after 60 minutes), a process completely blocked by endothelium removal or ramiprilat.
The endothelium is the critical site for angiotensin II production in the vascular wall and the primary target for ACE inhibitors.
The demonstration of all components of the renin-angiotensin system in vascular tissue has raised questions as to the precise location of the local angiotensin II generation within the vascular wall. We investigated the metabolism of angiotensin I to angiotensin II in the vascular wall in the isolated rabbit thoracic aorta. Angiotensin I (3 x 10(-9) M) applied into the aortic lumen was partially converted to angiotensin II (14% after 60 minutes), but most of the luminal angiotensin I was degraded to peptide fragments or diffused as intact angiotensin I, peptide fragments, or both, into the vessel wall. Incubation studies with 3Hangiotensin I revealed that angiotensin I or angiotensin I fragments mainly diffused into the medial layer of the aorta and to a lesser degree into the adventitia and the endothelium. After removal of the endothelium, angiotensin II generation could no longer be detected. Addition of the angiotensin converting enzyme inhibitor ramiprilat (10(-7) M) to the incubation medium led to a complete blockade of angiotensin II generation by endothelial angiotensin converting enzyme. Our results underline the importance of the endothelium for conversion of angiotensin I to angiotensin II and provide evidence that conversion of angiotensin I to angiotensin II is predominantly achieved by endothelial cells. They also support the concept of an endocrine versus autocrine/paracrine renin-angiotensin system where the endothelium of the vasculature is the critical target site for angiotensin II production by both systems and, thus, the most important site for the actions of angiotensin converting enzyme inhibitors.
Gohlke et al. (Sat,) reported a other. Angiotensin I and Ramiprilat was evaluated on Conversion of angiotensin I to angiotensin II. In isolated rabbit thoracic aorta, luminal angiotensin I was partially converted to angiotensin II (14% after 60 minutes), a process completely blocked by endothelium removal or ramiprilat.