Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Abstract

angiotensin II type 1 receptor (AT1R) blockers. These drugs block angiotensin II (Ang II) -the primary active peptide in the RAS, which has many effects on blood vessels, the heart, the brain and the kidneys -from activating AT1R. AT1R is one of the two well-characterized receptors that Ang II activates (in addition to angiotensin II type 2 receptor (AT2R)). 3 Losartan is an angiotensin receptor blocker, 4 which mainly antagonizes AT1R, while PD123319 can block AT2R and Mas-related G protein-coupled receptor D (MrgD) receptors. 5 Recently, numerous researchers have shown that the RAS has additional complex multifunctional peptides, enzymes and receptors. The discovery of the ACE2/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, 6,7 which counterbalances several functions of the ACE/Ang II/AT1R axis, has highlighted the complexity of the RAS. The ACE2/Ang-(1-7)/ Mas receptor axis acts as a counter-regulatory axis. 7 It involves the heptapeptide peptide known as Ang-(1-7), which acts through a G-protein-coupled receptor called Mas. 7 Ang-(1-7) can be hydrolyzed from Ang II by the action of peptidases such as ACE2 and prolyl endopepti-D espite major progress in the research on the pathogenesis and management of hypertension and other aspects of cardiometabolic disease, these conditions underlie a significant number cases of morbidity and mortality due to cardiovascular and chronic kidney disease. It is predicted that there will be an increase in the hypertension prevalence rate in the United States (US). Currently, this condition affects 29% of the population in this country; that is, ~65 million individuals. 1 The significance of the renin-angiotensin system (RAS) in the development of hypertension and cardiovascular disease is well known. 2 Chronic RAS activation is a significant causal factor associated with the gradual malfunction of organs such as blood vessels, the kidneys and the heart. 2 These consequences of RAS activation have encouraged the development of medicines that can deactivate the RAS and thereby prevent the associated pathologies. The first class of drugs aimed at RAS inhibition are known as angiotensin-converting enzyme (ACE1) inhibitors, and they came on the market in the late 1970 s. Background: Alamandine is a newly discovered component of the renin-angiotensin system, which regulates blood pressure. In this study, the effect of alamandine on cardiovascular parameters in two-kidney, one clip (2K1C) hypertensive rats and normotensive rats, and the possible roles of the angiotensin II type 1 receptor (AT1R) and the PD123319-sensitive receptors in mediating this effect was investigated.

Effect of Prolonged Infusion of Alamandine on Cardiovascular Parameters and Cardiac ACE2 Expression in a Rat Model of Renovascular Hypertension

“…An LVEDP level >16 mmHg has been considered to be a sign of left ventricular diastolic dysfunction. 20) Alamandine decreased LVEDP in hypertensive rats which is most likely a result of improved cardiac function after alamandine using. Improvement in heart function and cardiomyocyte hypertrophy was seen in Ang-(1-7)-treated mice.…”

“…9) Ang A can be hydrolyzed by ACE2 to generate alamandine, and alamandine can also be produced directly from Ang (1-7) by decarboxylation of its aspartate residue. 10) Alamandine and Ang (1-7) are also structurally similar; the only difference between these 2 peptides is the presence of alanine (in alamandine) in place of an aspartate residue in the amino terminus. They have similarity in most of their biological effects.…”

Protective Effect of Alamandine on Doxorubicin‑Induced Nephrotoxicity in Rats

“…Ang 1-7 induces vasodilator, natriuretic, and diuretic effects through the mas receptor. It has been suggested that alamandine, a heptapeptide with an Ang1-7-like structure, exhibits actions similar to Ang1-7 [5,[35][36][37].…”

Counter-regulatory renin–angiotensin system in cardiovascular disease

“…Initially, mean arterial pressure and left ventricular sys tolic pressure increased briefly in an AT 1 R dependent manner, followed by a reduction in these parameters, which persisted throughout the rest of the infusion period. This anti hypertensive effect was reversed by PD123319, an AT 2 R antagonist 68 . Additionally, alaman dine treatment mitigated vascular remodelling in mice subjected to transverse aortic constriction 69 .…”