ArticleJournal of the American Heart Association2014
Acute intravenous injection of serelaxin (recombinant human relaxin-2) causes rapid and sustained bradykinin-mediated vasorelaxation.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions.International journal of impotence research · 2024Article
- Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Pressurized Hot Water Extraction of Okra Seeds Reveals Antioxidant, Antidiabetic and Vasoprotective Activities.Plants (Basel, Switzerland) · 2021Article
- Antioxidant and Cytoprotective Effect of Quinoa (Antioxidants (Basel, Switzerland) · 2020Article
- Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model.International journal of molecular sciences · 2020Article
- The Novel Small-molecule Annexin-A1 Mimetic, Compound 17b, Elicits Vasoprotective Actions in Streptozotocin-induced Diabetic Mice.International journal of molecular sciences · 2020Article
- Relaxin reduces endothelium-derived vasoconstriction in hypertension: Revealing new therapeutic insights.British journal of pharmacology · 2020Article
- Relaxin 2 fails to lower intraocular pressure and to dilate retinal vessels in rats.International ophthalmology · 2019Article
- Relaxin activates AMPK-AKT signaling and increases glucose uptake by cultured cardiomyocytes.Endocrine · 2018Article
- Relaxin Deficiency Leads to Uterine Artery Dysfunction During Pregnancy in Mice.Frontiers in physiology · 2018Article
- Relaxin as a Therapeutic Target for the Cardiovascular Complications of Diabetes.Frontiers in pharmacology · 2018Review
- Vascular actions of relaxin: nitric oxide and beyond.British journal of pharmacology · 2017Review
- The actions of relaxin on the human cardiovascular system.British journal of pharmacology · 2017Review
- Serelaxin treatment reverses vascular dysfunction and left ventricular hypertrophy in a mouse model of Type 1 diabetes.Scientific reports · 2017Article
- Relaxin-2 in Cardiometabolic Diseases: Mechanisms of Action and Future Perspectives.Frontiers in physiology · 2017Review
- Serelaxin Treatment Reduces Oxidative Stress and Increases Aldehyde Dehydrogenase-2 to Attenuate Nitrate Tolerance.Frontiers in pharmacology · 2017Article
- G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention.Human reproduction update · 2016Review
- Serelaxin for the treatment of acute heart failure: a review with a focus on end-organ protection.European heart journal. Cardiovascular pharmacotherapy · 2016Review
- Time-dependent activation of prostacyclin and nitric oxide pathways during continuous i.v. infusion of serelaxin (recombinant human H2 relaxin).British journal of pharmacology · 2016Article
- Enhanced serelaxin signalling in co-cultures of human primary endothelial and smooth muscle cells.British journal of pharmacology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA recent clinical trial (RELAXin in Acute Heart Failure [RELAX-AHF]) demonstrated that 48 hours of continuous intravenous infusion of the vasorelaxant peptide serelaxin (recombinant human relaxin-2) to patients with acute heart failure reduced cardiovascular mortality at 180 days. The persistence of a vasorelaxant response as a potential mechanism for this long-term benefit and the vascular effects of a bolus intravenous injection of serelaxin have not been examined. This study investigates changes in resistance artery reactivity and passive mechanical wall properties following an intravenous serelaxin injection and whether these vascular effects persist in the absence of detectable circulating serelaxin. METHODS AND
resultsMale rats were injected with 13.3 μg/kg serelaxin into the tail vein; mesenteric arteries were assessed 3 and 24 hours after treatment by using wire-myography. Serelaxin increased basal nitric oxide synthase activity and reduced maximal contraction to endothelin-1 at 3 hours after administration. Serelaxin treatment also selectively enhanced bradykinin-mediated endothelium-dependent relaxation. This effect was sustained for 24 hours in the absence of circulating serelaxin. Serelaxin-mediated augmentation of bradykinin-evoked relaxation involved endothelium-derived hyperpolarization after 3 hours and prostacyclin-mediated relaxation after 24 hours. Furthermore, upregulation of inducible nitric oxide synthase, phosphorylation of protein kinase B at Ser473 and endothelial nitric oxide synthase at Ser1177 was observed at 24 hours after serelaxin injection. There were no effects of serelaxin on passive arterial wall stiffness.
conclusionOur data show that a bolus intravenous injection of serelaxin modulates endothelial vasodilator function 3 hours after administration, an effect that was sustained for 24 hours. The prolonged bradykinin-mediated vasorelaxation is principally mediated through prostacyclin.
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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.