alamandine and Atherosclerosis

The purpose of this review was to summarize the current knowledge on the role of angiotensin-(1-7) [Ang-(1-7)] and alamandine in experimental hypertension and atherosclerosis.. The renin-angiotensin system (RAS) is a very complex system, composed of a cascade of enzymes, peptides, and receptors, known to be involved in the pathogenesis of hypertension and atherosclerosis. Ang-(1-7), identified and characterized in 1987, and alamandine, discovered 16 years after, are the newest two main effector molecules from the RAS, protecting the vascular system against hypertension and atherosclerosis. While the beneficial effects of Ang-(1-7) have been widely studied in several experimental models of hypertension, much less studies were performed in experimental models of atherosclerosis. Alamandine has shown similar vascular effects to Ang-(1-7), namely, endothelial-dependent vasorelaxation mediated by nitric oxide and hypotensive effects in experimental hypertension. There are few studies on the effects of alamandine on atherosclerosis.

Topics: Angiotensin I; Animals; Atherosclerosis; Humans; Hypertension; Models, Theoretical; Oligopeptides; Peptide Fragments; Renin-Angiotensin System; Vasodilation

A primary peptide of the renin angiotensin system (RAS), Angiotensin (Ang) II, is a vasoconstrictor and promotor of atherosclerosis. To counter this, the RAS also consists of peptides and receptors which increase nitric oxide release from the endothelium and decrease nicotinamide adenine dinucleotide phosphate oxidase-related superoxide production. Two peptides, Ang (1-7) and alamandine are vasodilators, by activating the nitric oxide pathway via different receptors in the endothelium. Thus, herein we focus on the similarities and differences between alamandine and Ang (1-7) and the counterbalancing hypothesis on Ang II during endothelial dysfunction and atherosclerosis.

Topics: Angiotensin I; Animals; Atherosclerosis; Endothelium, Vascular; Humans; Nitric Oxide; Oligopeptides; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Signal Transduction; Vasodilation; Vasodilator Agents

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.

Topics: Acetylcholine; Angiotensin I; Angiotensins; Animals; Aorta, Abdominal; Aorta, Thoracic; Atherosclerosis; Carotid Arteries; Disease Models, Animal; Dose-Response Relationship, Drug; Iliac Artery; Male; Nitric Oxide Synthase Type III; Oligopeptides; Peptide Fragments; Phenylephrine; Rabbits; Receptors, G-Protein-Coupled; Renal Artery; Vasoconstriction; Vasodilation