Effect of nitric oxide and cyclooxygenase products on vascular resistance in dog and rat lungs.
Pulmonary vascular resistance decreases with increased cardiac output. Because nitric oxide (NO) and prostacyclin are potent vasodilators that are released with increased shear stress, their roles in the control of pulmonary vascular pressure were evaluated using isolated blood-perfused rat and dog lungs. Lungs were perfused with an initial arteriovenous pressure gradient (Ppa-Ppv) of 15 cmH2O; Ppa and Ppv were increased by the same amount, and the flow was measured. In rat lung (n = 6), the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) decreased pulmonary blood flow by approximately 50% at the same pressure (P < 0.05), whereas the cyclooxygenase inhibitor indomethacin (n = 6) had no effect. In dog lungs (n = 6), indomethacin decreased pulmonary blood flow by approximately 50% at the same pressure gradient (P < 0.05), whereas L-NAME (n = 6) had no effect. Furthermore, the flow increase that occurs as venous and arterial pressures are elevated together (so that Ppa-Ppv is constant) was inhibited by L-NAME in rat lungs and by indomethacin in dog lungs (P < 0.05 for each). Plasma guanosine 3',5'-cyclic monophosphate (cGMP) rose with increased absolute pressure in rat lung [from 71 +/- 17 to 274 +/- 104 pM (P < 0.05)], and this increase was blocked by L-NAME. Plasma cGMP was unchanged in dog lung, but the ratio of prostacyclin to thromboxane tended to be higher.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
J W
JW
Barnard
P S
PS
Wilson
T M
TM
Moore
W J
WJ
Thompson
A E
AE
Taylor
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D010477:Perfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin