ACE Inhibitors: Pharmacology

Gohlke, Peter

doi:10.1007/978-3-642-18497-0_17

Cited by 3 publications

(3 citation statements)

References 191 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are controversies about the effects of AT2R signaling, which are indicated in gray italic [3]. ARB angiotensin receptor blocker, AT1R angiotensin type one receptor, AT2R angiotensin type two receptor, AT3R angiotensin type three receptor, AT4R angiotensin type four receptor, CAGE chymostatin-sensitive angiotensin-II-generating enzyme, MasR Mas receptor, MMP-8 matrix metalloproteinase-8, NEP neutral endopeptidase, PCP prolyl carboxypeptidase, PEP prolyl endopeptidase, RAS renin-angiotensin system, VSMC vascular smooth muscle cell --group (i.e., enalapril, lisinopril, ramipril) that binds to side chains of the enzyme within the active moiety for improved potency and duration of action; and (3) drugs composed of phosphorus-containing ACEIs (i.e., fosinopril) [11,12]. Although direct ACEIs comparisons among available agents are rare, a Cochrane review has demonstrated that there are no clinically meaningful differences in BP-lowering efficacy between different ACEIs [13].…”

Section: Role Of Aceis In Cvd According To Current Guidelinesmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition: Beyond Blood Pressure Control—The Role of Zofenopril

Borghi

Omboni

2020

Adv Ther

View full text Add to dashboard Cite

The extensive use of angiotensin-converting enzyme inhibitors (ACEIs) as antihypertensive agents and the huge amount of data collected in clinical trials and post-marketing studies has allowed the extending of the indication of ACEIs beyond blood pressure control. Current guidelines recommend ACEIs in symptomatic patients with heart failure with reduced ejection fraction to decrease the risk of heart failure hospitalization, and also in patients after acute myocardial infarction (AMI) with ST-elevation with or without post-AMI ventricular dysfunction. Analyzing the association between the choice of an ACEI after AMI with the risk of mortality and re-infarction, a class effect, rather than the superiority of some agents, has been described. The focus of this review is centered on the role of ACEIs in addition to and beyond blood pressure control. It summarizes clinical evidence on the use of these agents in cardiovascular diseases, with a specific interest in the experience with zofenopril, which presents a peculiar pharmacological profile that may contribute to additional clinical benefits in some identifiable populations of patients. Indeed, the presence of a sulfhydryl group in its structure confers on zofenopril high anti-oxidant and anti-ischemic properties involving the activation of the H 2 S system, resulting in a cardioprotective effect. The efficacy and safety of zofenopril have been extensively evaluated and proved in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) program in numerous clinical settings. The pharmacological features and ancillary characteristics of zofenopril with potent cardioprotective effects seem to differentiate it from other ACEIs and to confer further benefits to patients.

show abstract

Section: Role Of Aceis In Cvd According To Current Guidelinesmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition: Beyond Blood Pressure Control—The Role of Zofenopril

Borghi

Omboni

2020

Adv Ther

View full text Add to dashboard Cite

show abstract

“…The relatively benign side effect profile of ACE inhibitors are summarized in Table 1. The potency of ACE inhibition is influenced by the drug’s affinity to interact with the zinc (Zn ++ ) ligand of the ACE [144]. There are three distinct chemical classes of ACE inhibitors.…”

Section: 0 Angiotensin Converting Enzyme Inhibitorsmentioning

confidence: 99%

“…Drugs containing a carboxyl group constitute most ACE inhibitors. These agents bind to side chains of the enzyme within the active moiety for improved potency and duration of action [144]. A third group of drugs composed of phosphorus-containing ACE inhibitors is represented by fosinopril [145, 146].…”

Section: 0 Angiotensin Converting Enzyme Inhibitorsmentioning

confidence: 99%

Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease

Ferrario

Mullick

2017

Pharmacological Research

101

View full text Add to dashboard Cite

A collective century of discoveries establishes the importance of the renin angiotensin aldosterone system in maintaining blood pressure, fluid volume and electrolyte homeostasis via autocrine, paracrine and endocrine signaling. While research continues to yield new functions of angiotensin II and angiotensin-(1-7), the gap between basic research and clinical application of these new findings is widening. As data accumulates on the efficacy of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers as drugs of fundamental importance in the treatment of cardiovascular and renal disorders, it is becoming apparent that the achieved clinical benefits is suboptimal and surprisingly no different than what can be achieved with other therapeutic interventions. We discuss this issue and summarize new pathways and mechanisms effecting the synthesis and actions of angiotensin II. The presence of renin-independent non-canonical pathways for angiotensin II production are largely unaffected by agents inhibiting renin angiotensin system activity. Hence, new efforts should be directed to develop drugs that can effectively block the synthesis and/or action of intracellular angiotensin II. Improved drug penetration into cardiac or renal sites of disease, inhibiting chymase –the primary angiotensin II forming enzyme in the human heart–, and/or inhibiting angiotensinogen synthesis would all be more effective strategies to inhibit the system. Additionally, given the role of angiotensin II in the maintenance of renal homeostatic mechanisms, any new inhibitor should possess greater selectivity of targeting pathogenic angiotensin II signaling processes and thereby limit inappropriate inhibition.

show abstract

Omapatrilat: penetration across the blood–brain barrier and effects on ischaemic stroke in rats

Günne

Zhao

Hedderich

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Omapatrilat (OMA), which simultaneously inhibits the angiotensin-converting enzyme (ACE) and the neutral endopeptidase (neprilysin (NEP)), is widely used in experimental protocols related to hypertension and heart failure. The penetration of OMA across the blood-brain barrier (BBB) and the effects of ACE/NEP inhibition on the recovery from ischaemic stroke have not yet been investigated. Angiotensin (Ang) I injected intracerebroventricularly (ICV) or intravenously (IV) is converted to Ang II by ACE and induces an immediate increase in blood pressure. The pressor responses to OMA administered ICV, orally or IV were studied in male Wistar rats instrumented with an ICV and arterial and venous catheters. OMA infused ICV rapidly appeared in the systemic circulation and more effectively attenuated the systemic than the central pressor responses to Ang I. OMA administered orally (5, 25, 100 μmol/kg body weight) or IV (0.5, 1, 5, 25 μmol/kg body weight) completely abolished increases in blood pressure to IV Ang I up to 2 h after treatment. The pressor responses to ICV Ang I were not altered, indicating that systemically administered OMA does not cross the BBB. To study the effects of ACE and NEP inhibition in the brain on the recovery from ischaemic stroke, OMA was infused ICV over a 5-day period before and 24 h after the occlusion of the middle cerebral artery (MCAO) for 90 min. ICV application of OMA had no effect on infarction volume and marginally improved neurological outcome. We demonstrate for the first time that simultaneous inhibition of ACE and NEP in the brain tissue does not alter the recovery from ischaemic stroke.

show abstract

ACE Inhibitors: Pharmacology

Cited by 3 publications

References 191 publications

Angiotensin-Converting Enzyme Inhibition: Beyond Blood Pressure Control—The Role of Zofenopril

Angiotensin-Converting Enzyme Inhibition: Beyond Blood Pressure Control—The Role of Zofenopril

Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease

Omapatrilat: penetration across the blood–brain barrier and effects on ischaemic stroke in rats

Contact Info

Product

Resources

About