angiotensin-a and alamandine

Renin angiotensin system (RAS) is an endogenous hormone system involved in the control of blood pressure and fluid volume. Dysregulation of RAS has a pathological role in causing cardiovascular diseases through hypertension. Among several key components of RAS, angiotensin peptides, varying in amino acid length and biological function, have important roles in preventing or promoting hypertension, cardiovascular diseases, stroke, vascular remodeling etc. These peptides are generated by the metabolism of inactive angiotensinogen or its derived peptides by hydrolyzing action of certain enzymes. Angiotensin II, angiotensin (1-12), angiotensin A and angiotensin III bind primarily to angiotensin II type 1 receptor and cause vasoconstriction, accumulation of inflammatory markers to sub-endothelial region of blood vessels and activate smooth muscle cell proliferation. Moreover, when bound to angiotensin II type 2 receptor, angiotensin II works as cardio-protective peptide and halt pathological cell signals. Other peptides like angiotensin (1-9), angiotensin (1-7), alamandine and angiotensin IV also help in protecting from cardiovascular diseases by binding to their respective receptors.

Topics: Angiotensin I; Angiotensin II; Angiotensin III; Angiotensinogen; Angiotensins; Animals; Blood Pressure; Humans; Hypertension; Oligopeptides; Peptide Fragments; Protective Factors; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Signal Transduction; Vasoconstriction

The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulations and its modulation is a challenging target for the vast majority of cardioprotective strategies. However, many biological effects of these drugs cannot be explained by the known mode of action. Our comprehension of the RAS is thus far from complete. The RAS represents an ingenious system of "checks and balances". It incorporates vasoconstrictive, pro-proliferative, and pro-inflammatory compounds on one hand and molecules with opposing action on the other hand. The list of these molecules is still not definitive because new biological properties can be achieved by minor alteration of the molecular structure. The angiotensin A/alamandine-MrgD cascade associates the deleterious and protective branches of the RAS. Its identification provided a novel clue to the understanding of the RAS. Angiotensin A (Ang A) is positioned at the "crossroad" in this system since it either elicits direct vasoconstrictive and pro-proliferative actions or it is further metabolized to alamandine, triggering opposing effects. Alamandine, the central molecule of this cascade, can be generated both from the "deleterious" Ang A as well as from the "protective" angiotensin 1-7. This pathway modulates peripheral and central blood pressure regulation and cardiovascular remodeling. Further research will elucidate its interactions in cardiovascular pathophysiology and its possible therapeutic implications.

Topics: Angiotensins; Cardiovascular Diseases; Humans; Oligopeptides; Receptors, G-Protein-Coupled

In this article, we review the recent findings regarding a new derivative of angiotensin-(1-7) [Ang-(1-7)], alamandine, and its receptor, the Mas-related G-coupled receptor type D (MrgD) with a special emphasis on its role and how it can be formed.. Over the last decade, there have been significant conceptual changes regarding the understanding of the renin-angiotensin system (RAS). A cardioprotective axis has been elucidated by the discovery of the Mas receptor for the biologically active Ang-(1-7), and the angiotensin-converting enzyme 2 (ACE2) that coverts Ang II into Ang-(1-7). In addition, several components of the system, such as Ang-(1-12), Angiotensin A (Ang A) and the newly discovered peptide, alamandine, have been identified. Alamandine is generated by catalysis of Ang A via ACE2 or directly from Ang-(1-7).. Alamandine is a vasoactive peptide with similar protective actions as Ang-(1-7) that acts through the MrgD and may represent another important counter-regulatory mechanism within the RAS.

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Angiotensins; Animals; Humans; Oligopeptides; Peptide Fragments; Peptidyl-Dipeptidase A; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Signal Transduction

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