Reduction of angiotensin A and alamandine vasoactivity in the rabbit model of atherogenesis: differential effects of alamandine and Ang(1-7).

Abstract

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 (eNOS), 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 eNOS. 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 eNOS. 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.

• Authors: Belthrand Habiyakare, Hiba Alsaadon, Michael L Mathai, Alan Hayes, Anthony Zulli
• Journal: International journal of experimental pathology (Int J Exp Pathol) Vol. 95 Issue 4 Pg. 290-5 (Aug 2014) ISSN: 1365-2613 [Electronic] England
• PMID: 24953785 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

Chemical References

• Angiotensins
• MRGPRD protein, human
• Oligopeptides
• Peptide Fragments
• Receptors, G-Protein-Coupled
• alamandine
• angiotensin A
• Phenylephrine
• Angiotensin I
• Nitric Oxide Synthase Type III
• angiotensin I (1-7)
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Angiotensin I (pharmacology)
• Angiotensins (physiology)
• Animals
• Aorta, Abdominal (drug effects, metabolism, physiopathology)
• Aorta, Thoracic (drug effects, metabolism, physiopathology)
• Atherosclerosis (metabolism, physiopathology)
• Carotid Arteries (drug effects, metabolism, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Iliac Artery (drug effects, metabolism, physiopathology)
• Male
• Nitric Oxide Synthase Type III (metabolism)
• Oligopeptides (pharmacology, physiology)
• Peptide Fragments (pharmacology)
• Phenylephrine (pharmacology)
• Rabbits
• Receptors, G-Protein-Coupled (metabolism)
• Renal Artery (drug effects, metabolism, physiopathology)
• Vasoconstriction (drug effects, physiology)
• Vasodilation (drug effects, physiology)