l-Lysine Decreases Nitric Oxide Production and Increases Vascular Resistance in Lungs Isolated from Lipopolysaccharide-Treated Neonatal Pigs

Carter, Barney W; Chicoine, Louis G.; Nelin, Leif D.

doi:10.1203/01.pdr.0000127722.55965.b3

Cited by 21 publications

(20 citation statements)

References 36 publications

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“…We chose to measure exNO production as a measure of total lung NO production. Although measurement of exNO does not differentiate airway vs. vascular sources of NO, we have previously found that in neonatal pigs the measurement of exNO production is a sensitive, rapidly responding measure of physiologically relevant total lung NO production (12). However, our use of whole lung homogenates limits our interpretation of these findings because of limitations in detecting changes in NO production and/or NOS levels localized to specific anatomic locations, such as lung epithelial cells and/or pulmonary vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…However, studies show that NO production can be increased by application of exogenous L-arginine, a phenomenon termed "the arginine paradox" (Arnal et al 1995;Wu and Meininger 2000). This effect can be attenuated by pretreatment with L-lysine (Tugba Durlu and Brading 2005) and L-lysine has also been shown to reduce NO production in isolated lung tissue (Carter et al 2004). An explanation may be a compartmentalization of NOS and its substrate, where the L-arginine pool is unavailable to the enzyme unless actively transported there.…”

Section: Discussionmentioning

confidence: 99%

The amino acid l-lysine blocks the disruptive effect of phencyclidine on prepulse inhibition in mice

et al. 2007

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L-lysine has been shown to block L-arginine transport in vitro, most likely via a competitive blockade and down regulation of cationic amino acid transporters. However, the importance of L-arginine transport as a regulatory mechanism in NO production in vivo is still not clear. The present results lend further support to the notion that some of the effects of PCP in the central nervous system are mediated via NO and that L-arginine transport may play a role in the regulation of NO production in the brain.

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“…In the isolated, perfused lung, exNO was measured as previously described (3,30). Briefly, 25 min after the equilibration of the system, the baseline exhaled gas was collected for 5 min into a mylar balloon attached to the ventilator exhaust port.…”

Section: Methodsmentioning

confidence: 99%

Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

Jin

Chen

Calvert

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (C(a)) in right ventricular work, a decrease in C(a) would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from L-arginine (L-Arg). However, little is known of the effect of L-Arg on vascular compliance (C(v)) in the lung. We hypothesized that exposure to CH would decrease C(a) and that this effect would be reversed by exogenous L-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R(0)). Hypoxia resulted in the expected increase in arterial resistance (R(a)) as well as a decrease in both C(a) and C(v). L-Arg had little effect on R(a), C(a), or C(v) in isolated lungs from normoxic animals. L-Arg decreased R(a) in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R(0), and L-Arg reversed this increase in R(0). L-Arg increased exhaled NO, and inhibition of L-Arg uptake attenuated the L-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in C(a) was reversed by L-Arg, suggesting that L-Arg may improve CH-induced right ventricular dysfunction.

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l-Lysine Decreases Nitric Oxide Production and Increases Vascular Resistance in Lungs Isolated from Lipopolysaccharide-Treated Neonatal Pigs

Cited by 21 publications

References 36 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

The amino acid l-lysine blocks the disruptive effect of phencyclidine on prepulse inhibition in mice

Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

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