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.

Koizumi T, Johnston D, Bjertnaes LJ, Banerjee MR, Newman JH
Exp Lung Res. 2002 28 (6): 473-84

PMID: 12217213 · DOI:10.1080/01902140290096737

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.

MeSH Terms (14)

6-Ketoprostaglandin F1 alpha Animals Endotoxemia Enzyme Inhibitors Hemodynamics Nitric Oxide Nitroarginine Oxygen Partial Pressure Prostaglandins Pulmonary Circulation Sheep Thromboxane B2 Vascular Resistance

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