ArticleBritish journal of pharmacology2008
Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 131 citations in OpenAlex.
- Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.Journal of clinical hypertension (Greenwich, Conn.) · 2018Trial
- Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).European journal of heart failure · 2013Trial
- Tumor-Selective Vascular Modulation by Acid-Cleavable Retro-Inverso Bradykinin Conjugates Enhances the Antitumor Efficacy of Nanomedicine.ACS omega · 2026Article
- Bradykinin Metabolism and Drug-Induced Angioedema.International journal of molecular sciences · 2023Review
- Picomolar Sensitivity Analysis of Multiple Bradykinin-Related Peptides in the Blood Plasma of Patients With Hereditary Angioedema in Remission: A Pilot Study.Frontiers in allergy · 2022Article
- Efficacy and safety of sacubitril/valsartan on heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.Frontiers in cardiovascular medicine · 2022Article
- Selective Inhibition of the C-Domain of ACE (Angiotensin-Converting Enzyme) Combined With Inhibition of NEP (Neprilysin): A Potential New Therapy for Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- A Robust Bioassay of the Human Bradykinin BPharmaceuticals (Basel, Switzerland) · 2021Review
- In Vitro Modeling of Bradykinin-Mediated Angioedema States.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme.Journal of medicinal chemistry · 2020Article
- Angiotensin-Converting Enzyme Inhibitor Protects Against Cisplatin Nephrotoxicity by Modulating Kinin B1 Receptor Expression and Aminopeptidase P Activity in Mice.Frontiers in molecular biosciences · 2020Article
- Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants.Frontiers in medicine · 2020Article
- Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.Pharmacological reviews · 2019Review
- Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction.Korean circulation journal · 2019Review
- Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors.BMC research notes · 2019Article
- Discovery of TD-0212, an Orally Active Dual Pharmacology ATACS medicinal chemistry letters · 2019Article
- Sacubitril/Valsartan: From Clinical Trials to Real-world Experience.Current treatment options in cardiovascular medicine · 2018Review
- Neprilysin Inhibitors and Bradykinin.Frontiers in medicine · 2018Review
- Comparing Pathways of Bradykinin Formation in Whole Blood From Healthy Volunteers and Patients With Hereditary Angioedema Due to C1 Inhibitor Deficiency.Frontiers in immunology · 2018Article
- D-ArgFrontiers in pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeInhibition of bradykinin metabolizing enzymes (BMEs) can cause acute angioedema, as demonstrated in a recent clinical trial in patients administered the antihypertensive, omapatrilat. However, the relative contribution of specific BMEs to this effect is unclear and confounded by the lack of a predictive pre-clinical model of angioedema. EXPERIMENTAL APPROACH: Rats were instrumented to record blood pressure and heart rate; inhibitors were infused for 35 min and bradykinin was infused during the last 5 min to elicit hypotension, as a functional marker of circulating bradykinin and relative angioedema risk. KEY
resultsIn the presence of omapatrilat bradykinin produced dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV (candoxatril+A-899301). However, hypotension was enhanced upon concomitant blockade of APP and further intensified in the presence of NEP inhibition to values not different from omapatrilat alone. CONCLUSIONS AND IMPLICATIONS: We demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE inhibition alone. Thus, novel BME inhibitors must display no activity against APP to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in patients with diabetes and cardiovascular disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.