Inhibition of endogenous nitric oxide during endotoxemia in awake sheep - effects of Nomega-nitro-l-arginine on the distribution of pulmonary vascular resistance and prostanoid products.
We examined the effects of endogenous nitric oxide (NO) inhibition on the longitudinal distribution of pulmonary vascular resistance and on arachidonic acid metabolism during endotoxemia in awake sheep. Mean pulmonary artery (Ppa), left atrial (Pla), and systemic artery pressure (Psa) were continuously measured, and cardiac output (CO) was continuously monitored by an implanted ultrasonic flow probe. We advanced a 7-French Swan-Ganz catheter into distal pulmonary artery and measured the pulmonary microwedge pressure (Pmw) with the balloon deflated, allowing calculation of upstream pulmonary vascular resistance (PVRup = [Ppa - Pmw]/CO) and down-stream PVR (PVRdown = [Pmw - Pla]/CO), respectively. In paired studies, endotoxin (1 micro g/kg) was infused over 30 minutes with and without N(omega)-nitro-L-arginine (NLA) treatment. NLA (20 mg/kg) was administered 30 minutes before endotoxin infusion. Endotoxin caused increases in PVRup and PVRdown. Pretreatment with NLA increases PVRup at baseline and enhanced increases in both PVRup and PVRdown during endotoxemia. Plasma level of thromboxane B(2) (TxB(2)) and prostacyclin (6-keto = PGF(1alpha)) significantly increased 1 hour after endotoxin administration (TxB(2), 308.3 +/- 94.8 [SE] to 2163.5 +/- 988.5 pg ml(-1), P <.05; 6-keto=PGF(1alpha), 155.6 +/- 91.4 to 564.9 +/- 131.8 pg ml(-1), P <.05), but the increased levels were similar to those in the NLA-pretreated animals. We conclude that endogenous NO mainly regulates precapillary vascular tone at baseline, and that NO modulated pre- and postcapillary vascular constriction during endotoxemia in sheep. It appears that cyclooxygenase production in response to endotoxin is unaffected by NO and its vascular effects.
Koizumi
Tomonobu
T
Center for Lung Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. tomonobu@hsp.md.shinshu-u.ac.jp
Johnston
David
D
Bjertnaes
Lars J
LJ
Banerjee
Meekule R
MR
Newman
John H
JH
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011453:Prostaglandins / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010100:Oxygen