ArticleBritish journal of pharmacology2010
The xanthine derivative KMUP-1 inhibits models of pulmonary artery hypertension via increased NO and cGMP-dependent inhibition of RhoA/Rho kinase.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 41 citations in OpenAlex.
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Activation of Nrf2 in Mice Causes Early Microvascular Cyclooxygenase-Dependent Oxidative Stress and Enhanced Contractility.Antioxidants (Basel, Switzerland) · 2022Article
- BKCells · 2021Article
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- rBMSC/Cav-1Stem cells international · 2019Article
- Review
- KMUP-1, a GPCR Modulator, Attenuates Triglyceride Accumulation Involved MAPKs/Akt/PPARγ and PKA/PKG/HSL Signaling in 3T3-L1 Preadipocytes.Molecules (Basel, Switzerland) · 2018Article
- Ripasudil Attenuates Lipopolysaccharide (LPS)-Mediated Apoptosis and Inflammation in Pulmonary Microvascular Endothelial Cells via ROCK2/eNOS Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- CYP2J2 metabolites, epoxyeicosatrienoic acids, attenuate Ang II-induced cardiac fibrotic response by targeting GαJournal of lipid research · 2017Article
- Restoration of uridine 5'-triphosphate-suppressed delayed rectifying KThe Kaohsiung journal of medical sciences · 2016Article
- Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways.Scientific reports · 2016Article
- Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice.International journal of molecular sciences · 2016Article
- Phosphodiesterase inhibitor KMUP-3 displays cardioprotection via protein kinase G and increases cardiac output via G-protein-coupled receptor agonist activity and Ca(2+) sensitization.The Kaohsiung journal of medical sciences · 2016Article
- Xanthine-based KMUP-1 improves HDL via PPARγ/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss.Journal of lipid research · 2015Article
- Buffered l-ascorbic acid, alone or bound to KMUP-1 or sildenafil, reduces vascular endothelium growth factor and restores endothelium nitric oxide synthase in hypoxic pulmonary artery.The Kaohsiung journal of medical sciences · 2015Article
- The Xanthine Derivative KMUP-1 Attenuates Serotonin-Induced Vasoconstriction and K⁺-Channel Inhibitory Activity via the PKC Pathway in Pulmonary Arteries.International journal of biological sciences · 2015Article
- Endothelial nitric oxide synthase-enhancing G-protein coupled receptor antagonist inhibits pulmonary artery hypertension by endothelin-1-dependent and endothelin-1-independent pathways in a monocrotaline model.The Kaohsiung journal of medical sciences · 2014Article
- A xanthine-derivative K(+)-channel opener protects against serotonin-induced cardiomyocyte hypertrophy via the modulation of protein kinases.International journal of biological sciences · 2013Article
- KMUP-1 inhibits hypertension-induced left ventricular hypertrophy through regulation of nitric oxide synthases, ERK1/2, and calcineurin.The Kaohsiung journal of medical sciences · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeKMUP-1 is known to increase cGMP, enhance endothelial nitric oxide synthase (eNOS) and suppress Rho kinase (ROCK) expression in smooth muscle. Here, we investigated the mechanism of action of KMUP-1 on acute and chronic pulmonary artery hypertension (PAH) in rats. EXPERIMENTAL APPROACH: We measured pulmonary vascular contractility, wall thickening, eNOS immunostaining, expressions of ROCK II, RhoA activation, myosin phosphatase target subunit 1 (MYPT1) phosphorylation, eNOS, soluble guanylyl cyclase (sGC), protein kinase G (PKG) and phosphodiesterase 5A (PDE-5A), blood oxygenation and cGMP/cAMP, and right ventricular hypertrophy (RVH) in rats. KEY
resultsIn rings of intact pulmonary artery (PA), KMUP-1 relaxed the vasoconstriction induced by phenylephrine (10 microM) or the thromboxane A(2)-mimetic U46619 (0.5 microM). In endothelium-denuded PA rings, this relaxation was reduced. In acute PAH induced by U46619 (2.5 microg x kg(-1) x min(-1), 30 min), KMUP-1 relaxed vasoconstriction by enhancing levels of eNOS, sGC and PKG, suppressing those of PDE-5A, RhoA/ROCK II activation and MYPT1 phosphorylation, and restoring oxygenation in blood and cGMP/cAMP in plasma. Incubating smooth muscle cells from PA (PASMCs) with KMUP-1 inhibited thapsigargin-induced Ca(2+) efflux and angiotensin II-induced Ca(2+) influx. In chronic PAH model induced by monocrotaline, KMUP-1 increased eNOS and reduced RhoA/ROCK II activation/expression, PA wall thickening, eNOS immunostaining and RVH. KMUP-1 and sildenafil did not inhibit monocrotaline-induced PDE-5A expression. CONCLUSION AND IMPLICATIONS: KMUP-1 decreased PAH by enhancing NO synthesis by eNOS, with consequent cGMP-dependent inhibition of RhoA/ROCK II and Ca(2+) desensitization in PASMCs. KMUP-1 has the potential to reduce vascular resistance, remodelling and RVH in PAH.
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.