On Endogenous Angiotensin II Antagonism in Hypertension

Ocaranza, María Paz; Jalil, Jorge

doi:10.1161/hypertensionaha.116.07471

Cited by 7 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More interestingly, repeated DPP III injection every other day for 4 weeks significantly attenuated ANG II-induced cardiac fibrosis and hypertrophy, albuminuria and kidney injury were significantly attenuated [46]. These results strongly suggest that DPP III may be a therapeutic target for ANG II-dependent hypertension and target organ damage [46,219]. …”

Section: New Insights Into the Roles And Therapeutic Implications mentioning

confidence: 99%

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

Zhang

Zhuo

2017

Pharmacological Research

365

323

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) is undisputedly one of the most prominent endocrine (tissue-to-tissue), paracrine (cell-to-cell) and intracrine (intracellular/nuclear) vasoactive systems in the physiological regulation of neural, cardiovascular, blood pressure, and kidney function. The importance of the RAS in the development and pathogenesis of cardiovascular, hypertensive and kidney diseases has now been firmly established in clinical trials and practice using renin inhibitors, angiotensin-converting enzyme (ACE) inhibitors, type 1 (AT1) angiotensin II (ANG II) receptor blockers (ARBs), or aldosterone receptor antagonists as major therapeutic drugs. The major mechanisms of actions for these RAS inhibitors or receptor blockers are mediated primarily by blocking the detrimental effects of the classic angiotensinogen/renin/ACE/ANG II/AT1/aldosterone axis. However, the RAS has expanded from this classic axis to include several other complex biochemical and physiological axes, which are derived from the metabolism of this classic axis. Currently, at least five axes of the RAS have been described, with each having its key substrate, enzyme, effector peptide, receptor, and/or downstream signaling pathways. These include the classic angiotensinogen/renin/ACE/ANG II/AT1 receptor, the ANG II/APA/ANG III/AT2/NO/cGMP, the ANG I/ANG II/ACE2/ANG (1–7)/Mas receptor, the prorenin/renin/prorenin receptor (PRR or Atp6ap2)/MAP kinases ERK1/2/V-ATPase, and the ANG III/APN/ANG IV/IRAP/AT4 receptor axes. Since the roles and therapeutic implications of the classic angiotensinogen/renin/ACE/ANG II/AT1 receptor axis have been extensively reviewed, this article will focus primarily on reviewing the roles and therapeutic implications of the vasoprotective axes of the RAS in cardiovascular, hypertensive and kidney diseases.

show abstract

Section: New Insights Into the Roles And Therapeutic Implications mentioning

confidence: 99%

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

Zhang

Zhuo

2017

Pharmacological Research

365

323

View full text Add to dashboard Cite

show abstract

“…For instance, lactate, the standard measure of tissue hypoxia, is a biomarker of organ failure that is too late . Circulating dipeptidyl peptidase 3 (cDPP3) is a protease involved in the degradation of angiotensin II and enkephalins . Recently, it has been shown that high values of cDPP3 were found in critically ill patients suffering from septic shock and CS .…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Circulating dipeptidyl peptidase 3 (cDPP3) is a protease involved in the degradation of angiotensin II and enkephalins. [16][17][18] Recently, it has been shown that high values of cDPP3 were found in critically ill patients suffering from septic shock 19 and CS. 20 We hypothesize that cDPP3 might be associated with alterations in haemodynamics and survival in CS patients.…”

Section: Introductionmentioning

confidence: 99%

Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial

Takagi

Blet

Lévy

et al. 2019

European J of Heart Fail

View full text Add to dashboard Cite

Aims Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of cardiovascular mediators. Its administration has been shown to be associated with impaired cardiac contraction and kidney haemodynamics while its inhibition restored cardiac contraction in a pre‐clinical model of severe heart failure in mice. Circulating DPP3 (cDPP3) was found to be elevated in shock. The present study aims to assess the association between cDPP3 and worsening haemodynamics, namely refractory shock, in a cohort of cardiogenic shock (CS). Methods and results This is an ancillary study of OptimaCC, a prospective, double‐blind, multicentre, randomized study assessing efficacy and safety of catecholamines in 57 patients with CS after acute myocardial infarction. cDPP3 was measured in plasma at inclusion, 24 h, 48 h, and 72 h, and haemodynamic and biological parameters were recorded at inclusion. cDPP3 values were higher in refractory CS than non‐refractory CS at inclusion (median [interquartile range]; 76.1 [37.9–238.7] ng/mL vs. 32.8 [23.9–47.6] ng/mL, P = 0.014), at 24 h (P < 0.001) and up to 48 h (P = 0.027). Furthermore, cDPP3 at inclusion discriminated CS patients who did develop refractory shock vs. non‐refractory with an area under the curve of 0.73 (95% confidence interval [CI] 0.55–0.92). The high cDPP3 group (cDPP3 ≥59.1 ng/mL) at inclusion had a higher Simplified Acute Physiology Score II (SAPS II), lower cardiac index and lower estimated glomerular filtration rate. More importantly, in CS patients with high cDPP3 at inclusion, those who rapidly decreased cDPP3 at 24 h exhibited a striking reduction in the occurrence of refractory shock and death. Conclusion In CS patients, cDPP3 gives an early prediction of outcome, including development of refractory status and/or survival. Clinical Trial Registration: http://clinicaltrials.gov Identifier NCT01367743

show abstract

“…ACE2 can also degrade Ang I to Ang 1-9 which can be further degraded by ACE to Ang 1-7. This peptide acts upon MAS receptors and opposes Ang II effects [28][29][30]. The most recent identified member of the vasodilatory axis of the RAS is alamandine.…”

Section: Systemic Renin Angiotensin System (Ras)mentioning

confidence: 99%

Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

Jahandideh

2020

IJMS

View full text Add to dashboard Cite

In addition to the regulation of blood pressure, the renin-angiotensin system (RAS) also plays a key role in the onset and development of insulin resistance, which is central to metabolic syndrome (MetS). Due to the interplay between RAS and insulin resistance, antihypertensive compounds may exert beneficial effects in the management of MetS. Food-derived bioactive peptides with RAS blocking properties can potentially improve adipose tissue dysfunction, glucose intolerance, and insulin resistance involved in the pathogenesis of MetS. This review discusses the pathophysiology of hypertension and the association between RAS and pathogenesis of the MetS. The effects of bioactive peptides with RAS modulating effects on other components of the MetS are discussed. While the in vivo reports on the effectiveness of antihypertensive peptides against MetS are encouraging, the exact mechanism by which these peptides infer their effects on glucose and lipid handling is mostly unknown. Therefore, careful design of experiments along with standardized physiological models to study the effect of antihypertensive peptides on insulin resistance and obesity could help to clarify this relationship.

show abstract

On Endogenous Angiotensin II Antagonism in Hypertension

Cited by 7 publications

References 10 publications

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

The vasoprotective axes of the renin-angiotensin system: Physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial

Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

Contact Info

Product

Resources

About