Next Article in Journal
PG-2, a Potent AMP against Pathogenic Microbial Strains, from Potato (Solanum tuberosum L cv. Gogu Valley) Tubers Not Cytotoxic against Human Cells
Next Article in Special Issue
Interplay between Hepatitis C Virus and Redox Cell Signaling
Previous Article in Journal
Molecular Typing of Mastitis-Causing Staphylococcus aureus Isolated from Heifers and Cows
Previous Article in Special Issue
Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells
Open AccessArticle

Cyclic Stretch Induces Inducible Nitric Oxide Synthase and Soluble Guanylate Cyclase in Pulmonary Artery Smooth Muscle Cells

Department of Pediatrics, Northwestern University, Chicago, IL 60611, USA
Department of Pediatrics, University of California, Davis, CA 95817, USA
Department of Pediatrics and Physiology, University of Buffalo, Buffalo, NY 14222, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(2), 4334-4348;
Received: 31 December 2012 / Revised: 12 February 2013 / Accepted: 17 February 2013 / Published: 21 February 2013
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9% vs. 33.3 ± 5.7% maximal oxidation), as measured by the intracellular redox sensor roGFP. Cyclic stretch also increased sGCβ protein expression (2.5 ± 0.9-fold), sGC activity (1.5 ± 0.2-fold) and cGMP levels (1.8 ± 0.2-fold), as well as iNOS mRNA and protein expression (3.0 ± 0.9 and 2.6 ± 0.7-fold, respectively) relative to control cells. An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity. Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls. In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs. The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension. View Full-Text
Keywords: pulmonary vasculature; cyclic stretch; sGC; reactive oxygen species; iNOS pulmonary vasculature; cyclic stretch; sGC; reactive oxygen species; iNOS
MDPI and ACS Style

Shah, M.R.; Wedgwood, S.; Czech, L.; Kim, G.A.; Lakshminrusimha, S.; Schumacker, P.T.; Steinhorn, R.H.; Farrow, K.N. Cyclic Stretch Induces Inducible Nitric Oxide Synthase and Soluble Guanylate Cyclase in Pulmonary Artery Smooth Muscle Cells. Int. J. Mol. Sci. 2013, 14, 4334-4348.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Search more from Scilit
Back to TopTop