ArticleCritical care medicine2009
The Rho-A/Rho-kinase pathway is up-regulated but remains inhibited by cyclic guanosine monophosphate-dependent mechanisms during endotoxemia in small mesenteric arteries.
Article in Critical care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
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- Transcriptional Suppression of CPI-17 Gene Expression in Vascular Smooth Muscle Cells by Tumor Necrosis Factor, Krüppel-Like Factor 4, and Sp1 Is Associated with Lipopolysaccharide-Induced Vascular Hypocontractility, Hypotension, and Mortality.Molecular and cellular biology · 2019Article
- Impaired Ca(2+) Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia.Inflammation · 2016Article
- Attenuated platelet aggregation in patients with septic shock is independent from the activity state of myosin light chain phosphorylation or a reduction in Rho kinase-dependent inhibition of myosin light chain phosphatase.Intensive care medicine experimental · 2015Article
- Calcium desensitisation in late polymicrobial sepsis is associated with loss of vasopressor sensitivity in a murine model.Intensive care medicine experimental · 2015Article
- Redox signaling and splicing dependent change in myosin phosphatase underlie early versus late changes in NO vasodilator reserve in a mouse LPS model of sepsis.American journal of physiology. Heart and circulatory physiology · 2015Article
- Heparin inhibits angiotensin II-induced vasoconstriction on isolated mouse mesenteric resistance arteries through Rho-A- and PKA-dependent pathways.Vascular pharmacology · 2013Article
- Article
- The suppression of myosin light chain (MLC) phosphorylation during the response to lipopolysaccharide (LPS): beneficial or detrimental to endothelial barrier?Journal of cellular physiology · 2011Article
- Wound contraction is attenuated by fasudil inhibition of Rho-associated kinase.Plastic and reconstructive surgery · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveWe investigated whether a reduced activity in the Rho-A/Rho-kinase pathway could be involved in the impaired vascular reactivity observed in septic shock.
designEx vivo animal study.
settingUniversity research laboratory. SUBJECTS: Male Wistar rats.
interventionsRats received an intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg) either 6 or 24 hours before the onset of our experiments. The effects of Y-27632 (a Rho-kinase inhibitor) were assessed in first-order mesenteric rings taken from these animals using wire myograph. The expression of Rho-A, Rho-kinases I and II, and the total and phosphorylated myosin phosphatase targeting subunit 1 (MYPT1) were assessed by Western blotting. MEASUREMENTS AND MAIN
resultsThe EC50 to Y-27632 was reduced from 2.10 microM (1.22-3.66 microM) (control) to 0.21 microM (0.09-0.44 microM), and 9.54 (0.82-110.30) nM in LPS-treated groups 6 and 24 hours, respectively. The increased potency of Y-27632 was partially reversed by endothelium removal at both 6 and 24 hours. Incubation of Nomega-nitro-l-arginine methyl ester hydrochloride or 1400W (a nonselective and an inducible nitric oxide synthase inhibitor, respectively) normalized the responses to Y-27632 seen 6 hours after LPS. However, 1400W had no effect, whereas Nomega-nitro-l-arginine methyl ester hydrochloride caused a partial reduction in the enhanced potency of Y-27632 found 24 hours after LPS. The soluble guanylate cyclase inhibitor oxadiazolo[4,3-alpha]quinoxalin-1-one was able to bring the Y-27632 response back to normal both 6 and 24 hours after LPS. Rho-A, Rho-kinase I, Rho-kinase II, and MYPT1 were increased in mesenteric arteries from endotoxemic rats, but the phosphorylated MYPT1 was significantly reduced. However, incubation with oxadiazolo[4,3-alpha]quinoxalin-1-one circumvented the inhibition of MYPT1 phosphorylation found in preparations from LPS-treated animals.
conclusionsOur findings revealed an impaired Rho-A/Rho-kinase-mediated phosphorylation of MYPT1 in vessels from endotoxemic animals in a cyclic guanosine monophosphate-dependent manner, suggesting that changes in mechanisms involved in calcium sensitization play a pivotal role in cardiovascular changes observed in septic shock.
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