Key result
NO and NO donors relax pulmonary arteries with variable susceptibility to oxidative inactivation.
Why the study?
The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of inhaled nitric oxide and NO donors in pulmonary arteries was unclear.
In piglet pulmonary arteries, NO donors (SNAP, SNP) are less susceptible to inactivation by oxidative stress and oxyhaemoglobin compared to free NO, suggesting potential advantages in pulmonary hypertension therapy.
May inform NO donor selection for oxidative stress; leaves open clinical superiority over iNO in pulmonary hypertension.
Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) were analysed in isolated endothelium-denuded pulmonary arteries from 2-week-old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC(30)=7.73+/-0.12, 7.26+/-0.17 and 6.43+/-0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10(-6) M) or the sarcoplasmic Ca(2+)-ATPase thapsigargin (2x10(-6) M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3x10(-7) M) or diethyldithiocarbamate (1 mM) markedly inhibited NO- (pIC(30)=6.88+/-0.07 and 6.92+/-0.18, respectively), weakly inhibited SNAP- and had no effect on SNP-induced relaxation. Xanthine oxidase (5 mu ml(-1)) plus hypoxanthine (10(-4) M) markedly inhibited NO- (pIC(30)=6.96+/-0.12) but not SNAP- or SNP-induced relaxation. Superoxide dismutase (SOD), MnCl(2), diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC(30)=8.52+/-0.16, 8.23+/-0.11, 8.01+/-0.11 and 8.20+/-0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP- or SNP-induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.
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López‐López et al. (2001) studied Pulmonary hypertension model (isolated pulmonary arteries). Nitric oxide (NO) and NO donors (SNP, SNAP) was evaluated on Relaxation of arteries (pIC30). NO, SNAP, and SNP relaxed piglet pulmonary arteries (pIC30 7.73, 7.26, and 6.43, respectively), with NO donors showing differential susceptibility to scavenging by oxyhaemoglobin and superoxide.
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