scholarly journals Angiotensin-(1-7): Translational Avenues in Cardiovascular Control

2019 ◽  
Vol 32 (12) ◽  
pp. 1133-1142 ◽  
Author(s):  
Daniela Medina ◽  
Amy C Arnold
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Cardiovascular Control ◽  
Biologically Active ◽  
Global Public Health ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiovascular Actions

Abstract Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-angiotensin system. Of particular concern, uncontrolled activation of angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, angiotensin-(1–7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-angiotensin system. This hormone antagonizes angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1–7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of angiotensin-(1–7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of angiotensin-(1–7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.

scholarly journals Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
María Sánchez-Aguilar ◽  
Luz Ibarra-Lara ◽  
Leonardo Del Valle-Mondragón ◽  
María Esther Rubio-Ruiz ◽  
Alicia G. Aguilar-Navarro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
In Silico ◽  
Vascular Function ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Insulin Sensitizer ◽  
Angiotensin System ◽  
Renin Angiotensin

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

scholarly journals Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice

2019 ◽  
Vol 20 (1) ◽  
pp. 147032031983440 ◽  
Author(s):  
Zhongming Zhang ◽  
Yijing Zhang ◽  
Yan Wang ◽  
Shengchen Ding ◽  
Chenhui Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Subfornical Organ ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Peripheral Organs ◽  
Induced Hypertension ◽  
Basal Blood Pressure

Introduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/–), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin–angiotensin system components in the laminal terminalis and peripheral organs. Results: Nestin-BDNF (+/–) mice had lower renin–angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin–angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Conclusion: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin–angiotensin system molecules.

Coevolution of the rennin–angiotensin system and the nervous control of blood circulation

1984 ◽  
Vol 62 (2) ◽  
pp. 137-147 ◽  
Author(s):  
John X. Wilson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Blood Volume ◽  
Vascular Resistance ◽  
Renin Angiotensin System ◽  
Peripheral Vascular Resistance ◽  
Peripheral Vascular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

The mammalian renin–angiotensin system appears to be involved in the maintenance of blood volume and pressure because (i) sodium depletion, hypovolemia, and hypotension increase renin levels, and (ii) administration of exogenous angiotensin II rapidly increases mineralocorticoid and antidiuretic hormone production, transepithelial ion transport, drinking behavior, and peripheral vascular resistance. Are these also the physiological properties of the renin–angiotensin system in nonmammalian species? Signals for altered levels of renin activity have yet to be conclusively identified in nonmammalian vertebrates, but circulating renin levels are elevated by hypotension in teleost fish and birds. Systemic injection of angiotensin II causes an increase in arterial blood pressure in all the vertebrates studied, suggesting that barostatic control is a universal function of this hormone. Angiotensin II alters vascular tone by direct action on arteriolar muscles in some species, but at concentrations of the hormone which probably are unphysiological. More generally, angiotensin II increases blood pressure indirectly, by acting on the sympathetic nervous system. Catecholamines, derived from chromaffin cells and (or) from peripheral adrenergic nerves, mediate some portion of the vasopressor response to angiotensin II in cyclostomes, elasmobranchs, teleosts, amphibians, reptiles, mammals, and birds. Alteration of sympathetic outflow is a prevalent mechanism through which the renin–angiotensin system may integrate blood volume, cardiac output, and peripheral vascular resistance to achieve control of blood pressure and adequate perfusion of tissues.

Is angiotensin essential in drinking induced by water deprivation and caval ligation?

1981 ◽  
Vol 240 (1) ◽  
pp. R75-R80 ◽  
Author(s):  
M. C. Lee ◽  
T. N. Thrasher ◽  
D. J. Ramsay
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Water Intake ◽  
Water Deprivation ◽  
Essential Role ◽  
Vena Cava ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

The role of the renin-angiotensin system in drinking induced by water deprivation and caval ligation was assessed by infusion of saralasin into the lateral ventricles of rats. This technique was first validated by demonstrating its capability to specifically antagonize drinking to both systemic and central angiotensin II. However, neither the latency to drink nor the amount of water consumed following 24- or 30-h water deprivation was affected by saralasin. Furthermore, saralasin had no significant effect on the recovery of blood pressure or on the water intake following ligation of the abdominal vena cava. These observations suggest that the renin-angiotensin system alone does not play an essential role in the control of drinking following water deprivation or caval ligation in rats.

scholarly journals Involvement of the Intrarenal Renin-Angiotensin System in Experimental Models of Glomerulonephritis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Maki Urushihara ◽  
Yukiko Kinoshita ◽  
Shuji Kondo ◽  
Shoji Kagami
Keyword(s):  
Blood Pressure ◽  
Intracellular Signaling ◽  
Renin Angiotensin System ◽  
Experimental Models ◽  
At1 Receptor ◽  
Biologically Active ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Proinflammatory Mediators

The intrarenal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN). Angiotensin II (Ang II) is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN.

Effect of Administration of Sar1-Ala8-Angiotensin II during the Development and Maintenance of Renal Hypertension in the Rat

1978 ◽  
Vol 54 (6) ◽  
pp. 633-637 ◽  
Author(s):  
M. Fernandes ◽  
R. Fiorentini ◽  
G. Onesti ◽  
G. Bellini ◽  
A. B. Gould ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Early Phase ◽  
Left Kidney ◽  
Renal Hypertension ◽  
Renin Angiotensin System ◽  
Renal Arteries ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Origin

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin—angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

scholarly journals Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

2015 ◽  
Vol 309 (5) ◽  
pp. R444-R458 ◽  
Author(s):  
Annette D. de Kloet ◽  
Meng Liu ◽  
Vermalí Rodríguez ◽  
Eric G. Krause ◽  
Colin Sumners
Keyword(s):  
Blood Pressure ◽  
Glial Cell ◽  
Renin Angiotensin System ◽  
Cardiovascular Control ◽  
Health Concern ◽  
Ang Ii ◽  
Ongoing Research ◽  
Angiotensin System ◽  
Renin Angiotensin

Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.

C. The renin-angiotensin system. A history and review of the renin-angiotensin system

1969 ◽  
Vol 173 (1032) ◽  
pp. 317-325 ◽  
Keyword(s):  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Blood Stream ◽  
Biologically Active ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System A ◽  
Aldosterone Production ◽  
Pressor Agent

An outline of the development of knowledge of the renin-angiotensin system is given, and the nature of the enzyme renin, its site within the kidney as well as in other organs, and its action on plasma substrate to form first the decapeptide which is converted to the biologically active octapeptide, are considered. The methods of measurement of renin and angiotensin in body fluids are discussed and the factors causing increased or decreased secretion of renin into the blood stream related to physiological and pathological situations. The role of angiotensin as a pressor agent, vasoconstrictor and stimulator of aldosterone production is assessed in the light of current knowledge.

scholarly journals The renin-angiotensin system and its blockers

2014 ◽  
Vol 142 (11-12) ◽  
pp. 756-763 ◽  
Author(s):  
Rajko Igic ◽  
Ranko Skrbic
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Biologically Active ◽  
Kinin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Peptides ◽  
History Of ◽  
Essential Connection ◽  
Kallikrein Kinin System

Research on the renin-angiotensin system (RAS) has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE) metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS) and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma

1994 ◽  
Vol 131 (6) ◽  
pp. 582-588 ◽  
Author(s):  
Gen Yasuda ◽  
Hiroshi Shionoiri ◽  
Satoshi Umemura ◽  
Izumi Takasaki ◽  
Masao Ishii
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cushing’S Syndrome ◽  
Blood Pressure Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Cushing's Syndrome ◽  
Adrenocortical Adenoma ◽  
Angiotensin System ◽  
Renin Angiotensin

Yasuda G, Shionoiri H, Umemura S, Takasaki I, Ishii M. Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma. Eur J Endocrinol 1994:131:582–8 ISSN 0804–4643 We studied the roles played by the renin-angiotensin system in inducing hypertension in nine patients with Cushing's syndrome (CS) resulting from adrenocortical adenoma, and compared them with those in patients with primary aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension (EH). In the CS group, each parameter, including serum potassium, plasma renin activity, plasma aldosterone, deoxycorticosterone and corticosterone concentrations, is within the normal range. However, plasma renin activity in the CS group was lower than that in the RVH group but higher than that in the PA group, and plasma aldosterone concentration was lower than that in each RVH or PA group. These findings indicated that the CS group had a different type of hypertension from that in either RVH or PA, in which the renin angiotensin system or mineralocorticoids play an important role in hypertension. Meanwhile, captopril (50 mg) administration either with or without indomethacin pretreatment decreased the mean blood pressure in the CS group, although captopril failed to change it in the PA group or in normal subjects. Furthermore, the pressor response to exogenous angiotensin II in the CS group was higher than that in the RVH or EH group, but was not different from that in the PA group. Thus, the hypertension in patients with CS due to adrenocortical adenoma appears to be mediated through a change in the renin-angiotensin system in the form of exaggerated pressor responses to angiotensin II. G Yasuda, Second Department of Internal Medicine, Yokohama City University School of Medicine, 3-46 Urafune, Minami, Yokohama 232, Japan

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