title: C-Type Natriuretic Peptide Induces Anti-contractile Effect Dependent on Nitric Oxide, Oxidative Stress, and NPR-B Activation in Sepsis.
abstract: OBJECTIVE
  To evaluate the role of nitric oxide, reactive oxygen species (ROS), and natriuretic peptide receptor-B activation in C-type natriuretic peptide-anti-contractile effect on Phenylephrine-induced contraction in aorta isolated from septic rats.
  
  
  RESULTS
  Cecal ligation and puncture (CLP) surgery was used to induce sepsis in male rats. Vascular reactivity was conducted in rat aorta and resistance mesenteric artery (RMA). Measurement of survival rate, mean arterial pressure (MAP), plasma nitric oxide, specific protein expression, and localization were evaluated. Septic rats had a survival rate about 37% at 4 h after the surgery, and these rats presented hypotension compared to control-operated (Sham) rats. Phenylephrine-induced contraction was decreased in sepsis. C-type natriuretic peptide (CNP) induced anti-contractile effect in aortas. Plasma nitric oxide was increased in sepsis. Nitric oxide-synthase but not natriuretic peptide receptor-B expression was increased in septic rat aortas. C-type natriuretic peptide-anti-contractile effect was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation. Natriuretic peptide receptor-C, protein kinase-Cα mRNA, and basal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were lower in septic rats. Phenylephrine and CNP enhanced ROS production. However, stimulated ROS production was low in sepsis.
  
  
  CONCLUSIONS
  CNP induced anti-contractile effect on Phenylephrine contraction in aortas from Sham and septic rats that was dependent on nitric oxide-synthase, ROS, and natriuretic peptide receptor-B activation.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Laena
authors.initials: L
authors.lastname: Pernomian
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Prado
authors.affiliation: Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Bruno R
authors.initials: BR
authors.lastname: Silva
authors.affiliation: Department of Biomechanics, School of Medicine of Ribeirão Preto (FMRP), Medicine and Rehabilitation of the Locomotor System, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Azevedo
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pinheiro
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto (FMRP), University of São Paulo Ribeirão Preto, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
keywords: C-type natriuretic peptide; natriuretic peptide receptor B; nitric oxide; phenylephrine-induced contraction; reactive oxygen species; sepsis