Enhanced vascular PI3K/Akt-NOX signaling underlies the peripheral NMDAR-mediated pressor response in conscious rats.

ABSTRACT: The molecular mechanisms for peripheral N-methyl-D-aspartate receptor (NMDAR)-mediated vascular oxidative stress and pressor response are not known. We conducted integrative (in vivo) and ex vivo biochemical studies to test the hypothesis that reactive oxygen species (ROS)-dependent calcium influx, triggered by the activation of vascular kinases, underlies the NMDAR-mediated pressor response. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K)/Akt (wortmannin, 15 μg/kg), protein kinase C (chelerythrine: 5 mg/kg, intravenous), Ca²⁺ influx (nifedipine, 0.35 or 0.75 mg/kg), or NADPH oxidase (NOX: apocynin, 5 mg/kg) attenuated the peripheral NMDAR-mediated pressor response in conscious male Sprague-Dawley rats. NMDAR activation enhanced the phosphorylation of Akt, ERK1, JNK and p38

SUBMITTER: McGee MA 

PROVIDER: S-EPMC4013219 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature