Endogenous pulmonary nitric oxide in the regulation of airway microvascular 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.
Mehta
S
S
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Boudreau
J
J
Lilly
C M
CM
Drazen
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D006706:Homeostasis; D007262:Infusions, Intravenous; D008168:Lung / Q000201:enzymology; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology
D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester