Segmental pulmonary vascular responses to changes in pH in rat lungs: role of nitric oxide

Yj, Gao; Tassiopoulos, Apostolos K.; McGraw, Daniel J.; Hauser, Michael C.; Camporesi, Enrico M.; Hakim, T. S.

doi:10.1034/j.1399-6576.1999.430114.x

Cited by 17 publications

(12 citation statements)

References 31 publications

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“…An arterial site of action for K ϩ -induced constriction is consistent with previous studies in isolated lungs from adult rats (20,48). However, when the production of NO was inhibited, K ϩ caused a greater increase in arterial resistance in 14-day lungs than in the 7-day lungs.…”

Section: Discussionsupporting

confidence: 90%

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

Chicoine¹,

Paffett²,

Girton³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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September 7, 2007; doi:10.1152/ajplung.00235.2006 is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7-and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor N -nitro-L-arginine augmented the K ϩ -induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-dayold rats. Vasodilation to 0.1 M of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 M of the cGMP analog 8-(4-chlorophenylthio)guanosine-3Ј,5Ј-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels. nitric oxide synthase; pulmonary vascular resistance; isolated perfused lungs; soluble guanylyl cyclase; guanosine-3Ј,5Ј-cyclic monophosphate NITRIC OXIDE (NO) facilitates the transition from the highresistance low-flow fetal pulmonary circulation to the lowresistance high-flow pulmonary circulation found shortly after birth (1,15,35). Studies examining the ontogeny of endothelial nitric oxide synthase (eNOS) in the developing rat lung found that eNOS protein levels and mRNA levels are low in early gestation, increase severalfold in late gestation, and are greatest at the time of birth (29,38,49). Following birth, there is a decrease of eNOS protein and mRNA to the low levels found in the adult rat. A similar pattern of eNOS expression has also been described in the developing porcine lung by Hislop et al. (25) and in the developing ovine lung by Halbower et al. (23).Thus it is likely that elevated neonatal eNOS facilitates the transition from the high-resistance fetal pulmonary circulation to the low-resistance postnatal pulmonary circulation. Both, in vivo and in vitro studies have shown that eNOS expression is upregulated by several factors, including shear stress (39) and oxygen exposure (19,31,34). Furthermore, we have found that the effect of chronic hypoxia on eNOS expression is different in the neonatal vs. the adult rat lung (13,40). In the neonatal rat lung, eNOS protein levels decreased with chronic hypoxic exposure, whereas in the...

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Section: Discussionsupporting

confidence: 90%

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

Chicoine¹,

Paffett²,

Girton³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…An interatrial fenestration has been used to offset the potential negative effect of temporary increment of postoperative PVR resulting from lung injury related to the use of cardiopulmonary bypass (CPB) (5). However, if the shunt becomes extravagant, the resulting significant hypoxemia may lead to an even more severe pulmonary vasoconstriction due to resulting acid‐base disturbance (6). As a result, maintaining low postoperative PVR is an ultimate goal, and as such, various organs can be perfused with better‐oxygenated blood.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide in Conjunction With Milrinone Better Stabilized Pulmonary Hemodynamics After Fontan Procedure

Cai

Shi

et al. 2008

Artificial Organs

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Inhaled nitric oxide (iNO) has been used for patients with increased pulmonary vascular resistance (PVR) shortly after Fontan operation, but repeat deterioration of PVR during or shortly after its withdrawal remains a major concern. Milrinone, a phosphodiesterase type 3 (PDE3) inhibitor, can also reduce PVR for postoperative patients with pulmonary hypertension. We hypothesized that iNO, in conjunction with milrinone, can provide additive benefits for pulmonary hemodynamics and reduce the occurrence of iNO withdrawal failure/rebound. Thirty-one patients with marked elevation of transpulmonary pressure gradient (TPG, >10 mm Hg) or central venous pressure (CVP, >15 mm Hg) after modified fenestrated Fontan operation were prospectively randomized into two groups, that is, group iNO (iNO at approximately 10 ppm, n = 15) and group iNO + Mil (iNO at approximately 10 ppm and milrinone at 0.5 microg/kg/min, n = 16). Hemodynamics, arterial blood oxygenation, and occurrence of withdrawal failure/rebound were compared between the two groups. Combined application of iNO and milrinone resulted in (i) more significant decrement of CVP (19.6 +/- 3.5% in group iNO + Mil vs. 15.2 +/- 4.6% in group iNO, P < 0.05) and TPG (18.2 +/- 4.8% in group iNO + Mil vs. 15.3 +/- 2.6% in group iNO, P < 0.05), (ii) more significant increment of systolic systemic arterial pressure (8.7 +/- 2.7% in group iNO + Mil vs. 5.2 +/- 3.1% in group iNO, P < 0.05), and (iii) more significant improvement of arterial oxygen saturation (9.3 +/- 3.2% in group iNO + Mil vs. 6.8 +/- 2.8% in group iNO, P < 0.01). Occurrence of iNO withdrawal failure during its weaning or rebound after its discontinuation was significantly lower in group iNO + Mil. The combined use of iNO and milrinone provided additive benefits as compared with exclusive use of iNO for patients with elevated PVR after Fontan procedure.

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“…Perfusate acidosis leading to vasoconstriction of small arteries increasing PVR is a well-described phenomenon in models of isolated lung perfusion. 28 Rather than repeated administration of sodium bicarbonate, which tends to lead to increasing sodium levels in the perfusate, adjustment of the gas flow rate is used to effectively titrate PCO 2 and pH levels. 3.…”

Section: Ventilation-perfusion Interactions During Evlpmentioning

confidence: 99%

Technique for Prolonged Normothermic Ex Vivo Lung Perfusion

Cypel

Yeung

Hirayama

et al. 2008

The Journal of Heart and Lung Transplantation

459

417

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Segmental pulmonary vascular responses to changes in pH in rat lungs: role of nitric oxide

Cited by 17 publications

References 31 publications

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

Nitric Oxide in Conjunction With Milrinone Better Stabilized Pulmonary Hemodynamics After Fontan Procedure

Technique for Prolonged Normothermic Ex Vivo Lung Perfusion

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