Local formation of angiotensin II in the rat aorta: effect of endothelium.
1. The local formation of angiotensin II (AII) from its precursors, angiotensin I (AI) and tetradecapeptide (TDP) renin substrate, was studied in intact (with endothelium) and rubbed (without endothelium) aortic rings of the rat. 2. AI and TDP renin substrate maximally contracted intact tissues in a similar way to AII. The same observations were made in rubbed tissues. 3. The maximal response and the sensitivity of the aorta to these agonists were greater in rubbed than in intact tissues. 4. In intact preparations, methylene blue increased the contractile response to AII and TDP to the same extent as endothelium removal. 5. In intact preparations, AII receptor blockade completely suppressed all contractile responses, converting enzyme inhibition completely blocked the responses to AI and TDP, and renin inhibition partially blocked the responses to TDP. 6. In rubbed preparations, AII receptor blockade completely inhibited all contractile responses, converting enzyme inhibition completely suppressed the responses to AI but only partially inhibited those to TDP, and renin inhibition partially blocked the responses to TDP. 7. In conclusion, the formation of AII from TDP and its blockade by a converting enzyme inhibitor and a renin inhibitor shows that converting enzyme and a renin-like aspartic proteinase are present in the aortic wall. Furthermore, the results show that the endothelium is not essential for the conversion of the TDP to AII, but modulates the responses to locally formed AII through the release of endothelium-derived relaxing factor (EDRF).
Department of Cardiovascular Research, Ciba-Geigy Ltd., Basel, Switzerland.
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D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000808:Angiotensinogen / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism
D000808:Angiotensinogen; D000804:Angiotensin II; D009569:Nitric Oxide; D000803:Angiotensin I; D012083:Renin; D008751:Methylene Blue