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Relaxin renal

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https://www.readbyqxmd.com/read/29046312/relaxin-mediated-renal-vasodilation-in-the-rat-is-associated-with-falls-in-glomerular-blood-pressure
#1
Aihua Deng, Kirk P Conrad, Chris Baylis
Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory actions which are physiologically important during pregnancy. RLX also has potent antifibrotic actions and is being tested therapeutically in various fibrotic diseases including chronic kidney disease (CKD). Since renal vasodilation may expose the glomerulus to increased blood pressure (PGC), which exacerbates progression of CKD, we assessed the glomerular hemodynamic actions of RLX when administered acutely (75 min; 0.89 µg/100g body weight/hr, iv) and chronically (1...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28978531/effects-of-serelaxin-on-renal-microcirculation-in-rats-under-control-and-high-angiotensin-environments
#2
Weijian Shao, Carla B Rosales, Camila Gonzalez, Minolfa C Prieto, L Gabriel Navar
Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II infused male rats...
October 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28851937/serelaxin-improves-cardiac-and-renal-function-in-doca-salt-hypertensive-rats
#3
Dong Wang, Yuhuan Luo, Komuraiah Myakala, David J Orlicky, Evgenia Dobrinskikh, Xiaoxin Wang, Moshe Levi
Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830579/use-of-microcomputed-tomography-to-measure-the-relaxin-induced-expansion-of-intrapubic-ligaments-in-mice
#4
Heather A Zimmerman, Richard P Kennan, Chunlian Zhang, Kashmira Shah, Douglas G Johns, Joseph J Lynch, Maya Dajee
Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that μCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points...
August 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28688805/low-level-of-ochratoxin-a-affects-genome-wide-expression-in-kidney-of-pig
#5
Daniela Eliza Marin, Cornelia Braicu, Mihai Alexandru Gras, Gina Cecilia Pistol, Roxana Cojocneanu Petric, Ioana Berindan Neagoe, Mihai Palade, Ionelia Taranu
Ochratoxin A (OTA) is a mycotoxin produced by fungus belonging to Aspergillus and Penicillium genra. The aim of the present paper was to investigate if a low concentration OTA has toxic effect in pigs. Twelve piglets were fed with a control or an OTA (0.05 mg/kg feed) contaminated diet. After 30 days, animals were slaughtered and samples of blood and kidney were used for further analyses. The mycotoxin analyses showed a significant higher (6.25 times) concentration of OTA in the kidney of OTA intoxicated piglets than in control ones...
July 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28674260/relaxin-ameliorates-renal-fibrosis-and-expression-of-endothelial-cell-transition-markers-in-rats-of-isoproterenol-induced-heart-failure
#6
Gaoshu Zheng, Jiejie Cai, Xingxing Chen, Lingzhi Chen, Wenhua Ge, Xi Zhou, Hao Zhou
There may be cardio-renal interactions in rats of isoproterenol-induced heart failure, which may be associated with renal fibrosis and endothelial-to-mesenchymal transition (EndMT). Since its discovery, relaxin (RLX) which was regarded as a reproductive hormone for a long time, is recently considered an effective antifibrotic hormone in cardiac and renal fibrosis. We studied whether RLX diminished renal fibrosis in rats of isoproterenol (Iso)-induced heart failure and investigated the mechanism. Fifty male Sprague-Dawley rats were separated into five groups for treatment: control; Iso subcutaneously injection to induce heart failure, which led to renal fibrosis; RLX subcutaneously injection at low, medium and high dose (0...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28660304/differences-in-the-renal-antifibrotic-cgmp-cgki-dependent-signaling-of-serelaxin-zaprinast-and-their-combination
#7
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Lothar Faerber, Jens Schlossmann
Renal fibrosis is an important factor for end-stage renal failure. However, only few therapeutic options for its treatment are established. Zaprinast, a phosphodiesterase 5 inhibitor, and serelaxin, the recombinant form of the naturally occurring hormone relaxin, are differently acting modulators of cyclic guanosine monophosphate (cGMP) signaling. Both agents enhance cGMP availability in kidney tissue. These substances alone or in combination might interfere with the development of kidney fibrosis. Therefore, we compared the effects of combination therapy with the effects of monotherapy on renal fibrosis...
June 28, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28621254/use-of-microcomputed-tomography-to-measure-the-relaxin-induced-expansion-of-intrapubic-ligaments-in-mice
#8
Heather A Zimmerman, Richard P Kennan, Chunlian Zhang, Kashmira Shah, Douglas G Johns, Joseph J Lynch, Maya Dajee
Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that μCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points...
June 15, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28620300/novel-anti-fibrotic-therapies
#9
REVIEW
Benita L McVicker, Robert G Bennett
Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Novel treatments have recently been identified that hold promise as potential therapeutic agents for cardiovascular diseases associated with fibrosis, as well as other fibrotic conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28613403/opposite-actions-of-urotensin-ii-and-relaxin-2-on-cellular-expression-of-fibronectin-in-renal-fibrosis-a-preliminary-experimental-study
#10
LETTER
Valeria Cernaro, Maria A Medici, Federica Bianco, Domenico Santoro, Antonio Lacquaniti, Adolfo Romeo, Silvia Lucisano, Antoine Buemi, Michele Buemi
Our aim was to evaluate the role of urotensin II, urantide (urotensin II receptor antagonist) and relaxin-2 on the cellular expression of fibronectin as a surrogate marker for renal fibrosis. We employed LLC-PK1 renal tubular epithelial cells and assessed the influence on the fibrotic process of the above-mentioned substances by using anti-fibronectin antibodies in western blot analysis. The addition of urotensin II increased fibronectin expression. Urantide reduced the positivity for fibronectin caused by urotensin II (P<...
June 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28540295/relaxin-attenuates-contrast-induced-human-proximal-tubular-epithelial-cell-apoptosis-by-activation-of-the-pi3k-akt-signaling-pathway-in-vitro
#11
Xiang-Cheng Xie, Yizhi Cao, Xiu Yang, Qun-Hong Xu, Wei Wei, Ming Wang
Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms. Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28452195/serelaxin-in-addition-to-standard-therapy-in-acute-heart-failure-rationale-and-design-of-the-relax-ahf-2-study
#12
John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Peter S Pang, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A Hua, Thomas Severin, Marco Metra
Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180...
June 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28416741/relaxin-abrogates-renal-interstitial-fibrosis-by-regulating-macrophage-polarization-via-inhibition-of-toll-like-receptor-4-signaling
#13
Lei Chen, Ming-Lei Sha, Deng Li, Yi-Ping Zhu, Xing-Jie Wang, Chen-Yi Jiang, Shu-Jie Xia, Yi Shao
Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit the CKD process, it is important to prevent renal fibrosis, though CKD remains incurable. Renal fibrosis can be inhibited by relaxin in several experimental models, but the mechanism of relaxin for antifibrotic potential is still not clear. And here we have studied the role of relaxin in macrophage polarization and renal inflammation after unilateral ureteral obstruction (UUO). Our results show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling, shift macrophage polarization toward the M2 phenotype and ameliorat renal fibrosis in the early stages of UUO...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#14
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28009437/serelaxin-in-clinical-development-past-present-and-future
#15
REVIEW
Elaine Unemori
The availability of highly purified recombinant human relaxin, serelaxin, has allowed clinical trials to be conducted in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique haemodynamic properties that are likely to contribute to organ protection and long-term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#16
REVIEW
Raktim Kumar Ghosh, Kinjal Banerjee, Ramyashree Tummala, Somedeb Ball, Keyvan Ravakhah, Anjan Gupta
Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising healthcare costs and is one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long-term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy, but eventually found to have a number of other physiological actions, not only in pregnancy, but also in nonpregnant women and men...
February 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27707703/the-enigma-of-continual-plasma-volume-expansion-in-pregnancy-critical-role-of-the-renin-angiotensin-aldosterone-system
#17
REVIEW
Crystal A West, Jennifer M Sasser, Chris Baylis
Pregnancy is characterized by avid renal sodium retention and plasma volume expansion in the presence of decreased blood pressure. Decreased maternal blood pressure is a consequence of reduced systemic vascular tone, which results from an increased production of vasodilators [nitric oxide (NO), prostaglandins, and relaxin] and decreased vascular responsiveness to the potent vasoconstrictor (angiotensin II). The kidneys participate in this vasodilatory response, resulting in marked increases in renal plasma flow and glomerular filtration rate (GFR) during pregnancy...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27629886/serelaxin-improves-the-pathophysiology-of-placental-ischemia-in-the-reduced-uterine-perfusion-pressure-rat-model-of-preeclampsia
#18
Jose A Santiago-Font, Lorena M Amaral, Jessica Faulkner, Tarek Ibrahim, Venkata Ramana Vaka, Mark W Cunningham, Babbette LaMarca
Preeclampsia is a hypertensive disorder of pregnancy that has limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, currently, there is no preclinical evidence to support the use of relaxin during preeclampsia. Therefore, the goal of this study was to test the hypothesis that recombinant human relaxin-2 (Serelaxin, Novartis; RLX) could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability, and/or decrease prepro-endothelin-1 (PPET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) in the reduced uterine perfusion pressure (RUPP) model of preeclampsia...
December 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27590257/vascular-actions-of-relaxin-nitric-oxide-and-beyond
#19
REVIEW
C H Leo, M Jelinic, H H Ng, S A Marshall, J Novak, M Tare, K P Conrad, L J Parry
The peptide hormone relaxin regulates the essential maternal haemodynamic adaptations in early pregnancy through direct actions on the renal and systemic vasculature. These vascular actions of relaxin occur mainly through endothelium-derived NO-mediated vasodilator pathways and improvements in arterial compliance in small resistance-size arteries. This work catalysed a plethora of studies which revealed quite heterogeneous responses across the different regions of the vasculature, and also uncovered NO-independent mechanisms of relaxin action...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27489037/evidence-of-proteinuria-but-no-other-characteristics-of-pre-eclampsia-in-relaxin-deficient-mice
#20
Kelly P O'Sullivan, Sarah A Marshall, Scott Cullen, Tahnee Saunders, Natalie J Hannan, Sevvandi N Senadheera, Laura J Parry
Pre-eclampsia (PE) is a leading cause of maternal and fetal death, characterised by an imbalance of placental growth factors and hypertension at >20 weeks gestation. Impaired maternal systemic vascular adaptations and fetal growth restriction are features of both PE and pregnant relaxin-deficient (Rln-/-) mice. The aim of the present study was to investigate whether these phenotypes in Rln-/- mice are associated with abnormal placental growth factor expression, increased soluble fms-like tyrosine kinase-1 (sFlt-1), proteinuria and/or hypertension during pregnancy...
August 4, 2016: Reproduction, Fertility, and Development
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