EMAIL THIS PAGE TO A FRIEND

American journal of physiology. Regulatory, integrative and comparative physiology

Exposure of mice to chronic hypoxia attenuates pulmonary arterial contractile responses to acute hypoxia by increases in extracellular hydrogen peroxide.


PMID 24920729

Abstract

Exposing mice to a chronic hypoxic treatment (10% oxygen, 21 days) that promotes pulmonary hypertension was observed to attenuate the pulmonary vasoconstriction response to acute hypoxia (HPV) both in vivo and in isolated pulmonary arteries. Since catalase restored the HPV response in isolated arteries, it appeared to be attenuated by extracellular hydrogen peroxide. Chronic hypoxia promoted the detection of elevated lung superoxide, extracellular peroxide, extracellular SOD expression, and protein kinase G (PKG) activation [based on PKG dimerization and vasodilator-stimulated phosphoprotein (VASP) phosphorylation], suggesting increased generation of extracellular peroxide and PKG activation may contribute to the suppression of HPV. Aorta from mice exposed to 21 days of hypoxia also showed evidence for extracellular hydrogen peroxide, suppressing the relaxation response to acute hypoxia. Peroxide appeared to partially suppress contractions to phenylephrine used in the study of in vitro hypoxic responses. Treatment of mice with the heme precursor δ-aminolevulinic acid (ALA; 50 mg·kg(-1)·day(-1)) during exposure to chronic hypoxia was examined as a pulmonary hypertension therapy because it could potentially activate beneficial cGMP-mediated effects through promoting a prolonged protoporphyrin IX (PpIX)-elicited activation of soluble guanylate cyclase. ALA attenuated pulmonary hypertension, increases in both superoxide and peroxide, and the suppression of in vitro and in vivo HPV responses. ALA generated prolonged detectible increases in PpIX and PKG-associated phosphorylation of VASP, suggesting PKG activation may contribute to suppression of pulmonary hypertension and prevention of alterations in extracellular peroxide that appear to be attenuating HPV responses caused by chronic hypoxia.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2500976
Anti-SOD1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1406464
Anti-SOD1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA001401
Anti-SOD1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV45752
Anti-SOD1 antibody produced in rabbit, IgG fraction of antiserum
SAB5200083
Anti-SOD1 antibody produced in rabbit, 1 mg/mL, affinity isolated antibody
SAB1411305
Anti-SOD1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB4300467
Anti-VASP (Ab-157) antibody produced in rabbit, affinity isolated antibody
SAB4300436
Anti-VASP (Ab-239) antibody produced in rabbit, affinity isolated antibody
SAB1406577
Anti-VASP antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA005724
Anti-VASP antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
V3515
Anti-VASP antibody produced in rabbit, ~1.5 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB4503064
Anti-VASP antibody produced in rabbit, affinity isolated antibody
SAB4503065
Anti-VASP antibody produced in rabbit, affinity isolated antibody
129585
Maleimide, 99%
C4H3NO2
SAB1409700
Monoclonal Anti-SOD1 antibody produced in mouse, clone 10D5, purified immunoglobulin, buffered aqueous solution
M8010
N,N′-Dimethyl-9,9′-biacridinium dinitrate, used as chemiluminescent reagent
C28H22N4O6