title: In vivo upregulation of nitric oxide synthases in healthy rats.
abstract: Periodic acceleration (pGz), sinusoidal motion of the whole body in a head-foot direction in the spinal axis, is a novel noninvasive means for cardiopulmonary support and induction of pulsatile shear stress. pGz increases plasma nitrite levels, in vivo and in vitro. Additionally, pGz confers cardioprotection in models of ischemia reperfusion injury. We hypothesize that pGz may also confer a cardiac phenotypic change by upregulation of the expression of the various NO synthase (NOS) isoforms in vivo. pGz was applied for 1h to awake restrained male rats at 2 frequencies (360 and 600 cpm) and acceleration (Gz) of +/-3.4 m/s(2). pGz did not affect arterial blood gases or electrolytes. pGz significantly increased total nitrosylated protein levels, indicating increased NO production. pGz also increased mRNA and protein levels of eNOS and nNOS, and phosphorylated eNOS in heart. pGz increased Akt phosphorylation (p-AKT), but not total Akt, or phosphorylated ERK1/2. Inducible (i) NOS levels were undetectable with or without pGz. Immunoblotting revealed the localization of nNOS, exclusively in cardiomyocyte, and pGz increased its expression. We have demonstrated that pGz changes myocardial NOS phenotypes. Such upregulation of eNOS and nNOS was still evident 24h after pGz. Further studies are needed to understand the biochemical and biomechanical signal transduction pathway for the observed NOS phenotype changed induced by pGz.
authors.affiliation: Divisions of Neonatology, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Arias
authors.forename: Jorge
authors.initials: J
authors.lastname: Bassuk
authors.forename: Arkady
authors.initials: A
authors.lastname: Uryash
authors.forename: Paul
authors.initials: P
authors.lastname: Kurlansky
authors.forename: Keith
authors.initials: K
authors.lastname: Webster
authors.forename: Jose A
authors.initials: JA
authors.lastname: Adams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D004573:Electrolytes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000378:metabolism; D010766:Phosphorylation; D020543:Proteome / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D004573:Electrolytes; D020543:Proteome; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases