TY  - JOUR
T1  - NItric oxide and thromboxane a2–mediated pulmonary microvascular dysfunction
AU  - Wright JK, Kim LT, Rogers TE, Nguyen H, Turnage RH
Y1  - 1999/03/01
N1  - 10.1001/archsurg.134.3.293
JO  - Archives of Surgery
SP  - 293
EP  - 298
VL  - 134
IS  - 3
N2  - Objectives 
    To examine whether the lung releases nitric oxide (NO) in response to thromboxane A2 and to examine the local release of NO as a protective compensatory mechanism by which the lung responds to the proinflammatory and vasoactive effects of thromboxane A2.Design 
    The lungs of anesthetized Sprague-Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an inhibitor of NO synthase (nitroglycerine-nitro-L-arginine methyl ester [L-NAME]) (10−4 mol/L), an NO donor (sodium nitroprusside) (10−8 mol/L), or perfusate alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U-46619) (7.1×10−8 mol/L) was added to the perfusate. Fifteen minutes later, the capillary filtration coefficient, pulmonary arterial pressure, and vascular resistance were measured. Pulmonary NO release was assessed by quantitating the release of cyclic guanosine monophosphate into the perfusate.Results 
    The capillary filtration coefficient of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused with buffer alone (P<.05). The addition of sodium nitroprusside reduced the increase in capillary filtration coefficient associated with U-46619 by 50% (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused lung caused a 3.0±0.4 mm Hg increase in pulmonary artery pressure (P<.01) with a corresponding rise in total vascular resistance (P<.05). This effect was exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05). Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic guanosine monophosphate levels within the perfusate.Conclusion 
    These data are consistent with the hypothesis that NO release may be an important protective mechanism by which the lung responds to thromboxane A2.
SN  - 0004-0010
M3  - doi: 10.1001/archsurg.134.3.293
UR  - http://dx.doi.org/10.1001/archsurg.134.3.293
ER  -