Nitric oxide and thromboxane A2 modulate pulmonary pressure after ischemia and intestinal reperfusion.
BACKGROUND
Nitric oxide (NO) and thromboxane A(2) (TxA(2)) are paracrine substances that likely contribute to IR-induced lung injury. This study examined the hypothesis that pulmonary vasoconstriction during ischemia is induced by NO synthesis and ischemia/reperfusion (IR)-induced TxA(2).


METHODS
Wistar rats underwent 30 or 60 minute of intestinal ischemia with 60 minute of IR in situ. Sham-operated animals (Sham) served as the controls. After ischemia and IR or Sham, the pulmonary vessels were cannulated to perfuse the lungs with Krebs buffer in vitro. Pulmonary arterial (Ppa) and venous (Ppv) pressures were measured to calculate vascular resistance (Rt).


RESULTS
After baseline measurements, the nonselective inhibitor (N(omega)-nitro-L-arginine methyl ester), the selective nNOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM), TxA(2) synthase inhibitor imidazole or TxA(2)-receptor antagonist SQ-29,548 was added to the perfusate prior to measurements of Ppa, Ppv, and Ppc. The Rt was 73% greater in the injured group (P = .01). Pc of in the IR lungs was about twice that of controls (7.2 +/- 0.71 vs 2.43 +/- 0.36 mm Hg, respectively; P < .01). The nNOS inhibitor TRIM, imidazole, or SQ-29,548 reduced Rt by 45%, 33%, and 26%, respectively. IR-induced increases in Pc were reduced by addition of 500 mug/mL imidazole but not by lower doses of imidazole or SQ-29,548.


CONCLUSIONS
IR-induced pulmonary dysfunction is caused by increased vascular resistance and increased perfusion pressure. These changes are, at least in part, due to the ongoing release of TxA(2). Administration of 8Br-cGMP protected against TxA(2)-induced vasoconstriction.
Słupski
M
M
Department of Transplantology, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, ul. M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Toruń, Poland. maciejslupski@wp.pl
Szadujkis-Szadurska
K
K
Szadujkis-Szadurski
R
R
Szadujkis-Szadurski
L
L
Włodarczyk
Z
Z
Andruszkiewicz
J
J
Sinjab
A T
AT
D000818:Animals; D005260:Female; D007511:Ischemia; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D055370:Lung Injury; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013928:Thromboxane A2 / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2