Alterations in Nitric Oxide Production in 8-Week-Old Lambs with Increased Pulmonary Blood Flow

We studied the effects of administrating the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), or the nitric oxide precursor, L-arginine, on hemodynamic variables and serum nitrate concentrations in an anesthetized ovine model of endotoxemia to assess the effects on regional visceral blood flow and to determine whether L-arginine availability limits nitric oxide production. Animals received Escherichia coli endotoxin (2 micrograms/kg) followed 2 h later by L-NAME (25 mg/kg), L-arginine (0.575 g/kg), or saline administered over 1 h followed by an infusion of the same dose over 8 h (n = 6 per group). Renal and mesenteric blood flow were measured by placement of electromagnetic flow probes, and serum nitrate concentrations were determined using vanadium III chloride or nitrate reductase reduction to nitric oxide or nitrite, respectively. The results showed L-NAME significantly increased systemic vascular resistance (P < 0.01), decreased serum nitrate concentrations (P < 0.05), and caused a transient reduction in mesenteric blood flow (P < 0.05). L-Arginine caused a reduction in systemic vascular resistance (P < 0.01), increased mesenteric blood flow (P < 0.001) and conductance (P < 0.05). There were no significant changes in renal arterial blood flow in either group. We conclude that the availability of L-arginine limits nitric oxide production in endotoxemia and, furthermore, that L-arginine administration in this model causes significant mesenteric vasodilatation. L-NAME administration had only limited effect on visceral blood flow despite a marked increase in systemic vascular resistance and a reduction in nitric oxide production.

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Glucose-dependent insulinotropic peptide: differential effects on hepatic artery vs. portal vein endothelial cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00507.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. E773-E779 ◽

Cited By ~ 26

Author(s):

Ke-Hong Ding ◽

Qing Zhong ◽

Jianrui Xu ◽

Carlos M. Isales

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Blood Flow ◽

Portal Vein ◽

Hepatic Artery ◽

Cell Types ◽

Nitric Oxide Production ◽

Oxide Production ◽

Potent Vasoconstrictor ◽

Insulinotropic Peptide

Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.

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Nitric Oxide Modulation of Pulmonary Blood Flow Distribution in Lobar Hypoxia

Anesthesiology ◽

10.1097/00000542-199505000-00017 ◽

1995 ◽

Vol 82 (5) ◽

pp. 1216-1225 ◽

Cited By ~ 37

Author(s):

Filip Freden ◽

Shao Z. Wei ◽

Jan E. Berglund ◽

Claes Frostell ◽

Goran Hedenstierna

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Pulmonary Blood Flow ◽

Lower Lobe ◽

Nitric Oxide Production ◽

Nitric Oxide Synthase Inhibitor ◽

Endogenous Nitric Oxide ◽

Nitric Oxide Inhalation ◽

Synthase Inhibitor ◽

Oxide Synthase

Background Nitric oxide, endogenously produced or inhaled, has been shown to play an important role in the regulation of pulmonary blood flow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production increases the pulmonary vascular response to hypoxia. This study was performed to investigate the hypothesis that intravenous administration of an nitric oxide synthase inhibitor and regional inhalation of nitric oxide can markedly alter the distribution of pulmonary blood flow during regional hypoxia. Methods Hypoxia (5% O2) was induced in the left lower lobe of the pig, and the blood flow to this lobe was measured with transit-time ultrasound. Nitric oxide was administered in the gas ventilating the hypoxic lobe and the hyperoxic lung regions with and without blockade of endogenous nitric oxide production by means of N omega-nitro-L-arginine methyl ester (L-NAME). Results Hypoxia in the left lower lobe reduced blood flow to that lobe to 27 +/- 3.9% (mean +/- SEM) of baseline values (P < 0.01). L-NAME caused a further reduction in lobar blood flow in all six animals to 12 +/- 3.5% and increased arterial oxygen tension (PaO2) (P < 0.01). Without L-NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flow to 66 +/- 5.6% of baseline (P < 0.01) and, with L-NAME, nitric oxide delivered to the hypoxic lobe resulted in a lobar blood flow that was 88 +/- 9.3% of baseline (difference not significant). When nitric oxide was administered to the hyperoxic lung regions, after L-NAME infusion, the blood flow to the hypoxic lobe decreased to 2.5 +/- 1.6% of baseline and PaO2 was further increased (P < 0.01). Conclusions By various combinations of nitric oxide inhalation and intravenous administration of an nitric oxide synthase inhibitor, lobar blood flow and arterial oxygenation could be markedly altered during lobar hypoxia. In particular, the combination of intravenous L-NAME and nitric oxide inhalation to the hyperoxic regions almost abolished perfusion of the hypoxic lobe and resulted in a PaO2 that equalled the prehypoxic values. This possibility of adjusting regional blood flow and thereby of improving PaO2 may be of value in the treatment of patients undergoing one-lung ventilation and of patients with acute respiratory failure.

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