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Reduction of angiotensin A and alamandine vasoactivity in the rabbit model of atherogenesis: differential effects of alamandine and A ng(1‐7)
Author(s) -
Habiyakare Belthrand,
Alsaadon Hiba,
Mathai Michael L.,
Hayes Alan,
Zulli Anthony
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12087
Subject(s) - endocrinology , medicine , aorta , abdominal aorta , vasodilation , enos , vasoconstriction , angiotensin ii , acetylcholine , phenylephrine , nitric oxide , receptor , nitric oxide synthase , blood pressure
Summary Novel treatments are necessary to reduce the burden of cardiovascular disease ( CVD ). Alamandine binds to MrgD and is reported to induce vasodilation via stimulation of endothelial nitric oxide synthase (e NOS ), but its role in atherogenic blood vessels is yet to be determined. To determine the vasoactive role of alamandine and its precursor AngA in diseased aorta, New Zealand White rabbits were fed a diet containing 1% methionine + 0.5% cholesterol + 5% peanut oil for 4 weeks ( MC , n = 5) or control ( n = 6). In abdominal aorta, alamandine (1 μM) was added 30 min before a dose–response curve to angiotensin II or AngA (1 nM–1 μM), and immunohistochemistry was used to identify MrgD receptors and e NOS . The thoracic aorta, renal, carotid and iliac arteries were mounted in organ baths. Rings were precontracted with phenylephrine, then a bolus dose of alamandine (1 μM) was added 10 min before a dose–response curve to acetylcholine (0.01 μM–10 μM). The MrgD receptor was localized to normal and diseased aorta and colocalized with e NOS . In control but not diseased blood vessels, alamandine enhanced acetylcholine‐mediated vasodilation in the thoracic aorta and the iliac artery ( P < 0.05) and reduced it in the renal artery ( P < 0.05). In control abdominal aorta, AngA evoked less desensitization than AngII ( P < 0.05) and alamandine reduced AngA‐mediated vasoconstriction ( P < 0.05). In MC , AngA constriction was markedly reduced vs . control ( P < 0.05). The vasoactivity of alamandine and AngA are reduced in atherogenesis. Its role in the prevention of CVD remains to be validated.