scholarly journals Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation.

Circulation ◽  
1993 ◽  
Vol 88 (6) ◽  
pp. 2884-2887 ◽  
Author(s):  
S Rimar ◽  
C N Gillis
Keyword(s):  
Nitric Oxide ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasodilation ◽  
Selective Pulmonary Vasodilation

Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats

1996 ◽  
Vol 271 (6) ◽  
pp. L981-L986 ◽  
Author(s):  
A. Holzmann ◽  
K. D. Bloch ◽  
L. S. Sanchez ◽  
G. Filippov ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Sepsis Syndrome ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasculature ◽  
Cyclic Monophosphate ◽  
Pulmonary Vasodilation ◽  
Lps Challenge ◽  
And Control ◽  
Selective Pulmonary Vasodilation

Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis syndrome often accompanies a decreased response to iNO, we investigated NO responsiveness in isolated, perfused lungs from rats exposed to lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5 mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619. Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS-pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs at each concentration). The diminished vasodilatory response to iNO was associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not differ in lung extracts from LPS-pretreated and control rats. LPS increased pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS-pretreated rats less than lungs from control rats. In contrast, the PDE-insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate vasodilated lungs equally from both groups. After LPS challenge, the rat pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO appears partly attributable to increased pulmonary cGMP-PDE activity.

Search for an animal model to investigate selective pulmonary vasodilation

2016 ◽  
Vol 51 (4) ◽  
pp. 376-387
Author(s):  
Bodil Petersen ◽  
Thilo Busch ◽  
Katharina Noreikat ◽  
Lorenz Homeister ◽  
Ralf Regenthal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Animal Models ◽  
Vascular Tone ◽  
Acute Hypoxia ◽  
Haemodynamic Instability ◽  
Time Interval ◽  
Systemic Hypotension ◽  
Pulmonary Vasodilation ◽  
Selective Pulmonary Vasodilation

Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation. To do so, a haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration deemed to be a sufficient time interval before and after a possible intervention. In anaesthetized and mechanically-ventilated Sprague–Dawley rats pulmonary hypertension was induced either by acute hypoxia due to reduction of the inspired oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were instrumented to measure right ventricular and systemic arterial pressures. Acute hypoxia caused a short, and only transient, increase of pulmonary artery pressure as well as profound systemic hypotension which suggested haemodynamic instability. U46619 infusion induced variable changes in the pulmonary and systemic vascular tone without sufficient stabilization within 30 min. MCT provoked sustained pulmonary hypertension with normal systemic pressure values and inhalation of nitric oxide caused selective pulmonary vasodilation. In conclusion, out of the three examined rat animal models only MCT-induced pulmonary hypertension is a solid and reliable model for investigating selective pulmonary vasodilation.

Site of Pulmonary Vasodilation by Inhaled Nitric Oxide in Microembolic Lung Injury

1997 ◽  
Vol 156 (1) ◽  
pp. 75-85 ◽  
Author(s):  
CHRISTIAN MÉLOT ◽  
FRANÇOISE VERMEULEN ◽  
MARCO MAGGIORINI ◽  
ERIC GILBERT ◽  
ROBERT NAEIJE
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasodilation

Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung

1995 ◽  
Vol 78 (5) ◽  
pp. 1745-1749 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis
Keyword(s):  
Nitric Oxide ◽  
Vascular Occlusion ◽  
Inhaled Nitric Oxide ◽  
Krebs Solution ◽  
Total Resistance ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Perfused Lung ◽  
Occlusion Technique ◽  
Inhaled No

To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5–1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l–1.min; P < 0.01]. Acetylcholine infusion (ACh; 2–5 nmol/min) and nitroglycerin (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well.

Additive Effect of Beraprost on Pulmonary Vasodilation by Inhaled Nitric Oxide in Children With Pulmonary Hypertension

1997 ◽  
Vol 80 (5) ◽  
pp. 662-664 ◽  
Author(s):  
Fukiko Ichida ◽  
Kei-ichiro Uese ◽  
Shin-ichi Tsubata ◽  
Ikuo Hashimoto ◽  
Yuji Hamamichi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Inhaled Nitric Oxide ◽  
Additive Effect ◽  
Pulmonary Vasodilation

Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation

2001 ◽  
Vol 95 (1) ◽  
pp. 102-112 ◽  
Author(s):  
Kristina Hambraeus-Jonzon ◽  
Luni Chen ◽  
Filip Fredén ◽  
Peter Wiklund ◽  
Göran Hedenstierna
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Inhaled Nitric Oxide ◽  
No Production ◽  
Pulmonary Vasodilation ◽  
Distant Effect ◽  
Nitric Oxide Concentration ◽  
Fraction Of Inspired Oxygen

Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. Methods Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. Results Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P &lt; 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P &lt; 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P &lt; 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P &lt; 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P &lt; 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P &lt; 0.05), but more so in hypoxic (P &lt; 0.01) than in hyperoxic (P &lt; 0.05) lung regions, resulting in a further redistribution (P &lt; 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions. Conclusions Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

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