Key result
Systemic L-NAME reduced expired NO by 70% (P<0.01) and airway microvascular leak by up to 92% (P<0.05) in guinea pigs, whereas the type II NOS inhibitor aminoguanidine had no effect on leak.
Why the study?
Does NOS inhibition reduce expired NO levels and airway microvascular leak in guinea pigs?
Does NOS inhibition reduce expired NO levels and airway microvascular leak in guinea pigs?
Endogenous pulmonary nitric oxide contributes to both basal and antigen-stimulated airway microvascular leak in guinea pigs, an effect that does not appear to be mediated by type II NOS.
Caution against clinical translation of NOS inhibition; extends animal evidence for constitutive NOS in airway leak.
Endogenous nitric oxide (NO) is an important modulator of airway function, but its role in the regulation of airway microvascular leak (AMVL) remains unclear. Thus we assessed the effects of NO synthase (NOS) inhibition on expired NO (ENO) levels and on AMVL measured by the Evans blue dye technique in guinea pigs. In control unsensitized animals, systemic NG-nitro-L-arginine methyl ester (L-NAME) reduced ENO by 70 +/- 8% (P < 0.01) and reduced AMVL by 92 +/- 1 and 44 +/- 17% (P < 0.05 for both) in the extrapulmonary and intrapulmonary airways, respectively. In animals sensitized and challenged with intratracheal antigen, markedly increased levels of AMVL and ENO were similarly attenuated by L-NAME. In contrast, aminoguanidine, a relatively selective type II NOS inhibitor, reduced ENO in both antigen-sensitized and control unsensitized animals by 39 +/- 3% (P < 0.01) but had no effect on AMVL. These data indicate that endogenous pulmonary NO contributes to both basal and antigen-stimulated levels of AMVL in guinea pigs and that this NO-dependent activity does not appear to be derived from type II NOS.
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Mehta et al. (1998) studied Airway microvascular leak. NOS inhibition (L-NAME and aminoguanidine) vs. Control was evaluated on Expired NO (ENO) levels and airway microvascular leak (AMVL) (p=<0.05). Systemic L-NAME reduced expired NO by 70% (P<0.01) and airway microvascular leak by up to 92% (P<0.05) in guinea pigs, whereas the type II NOS inhibitor aminoguanidine had no effect on leak.
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