The Role Of Endothelial Nitric Oxide Synthase Expression In The Development Of Pulmonary Hypertension In Chronically Hypoxic Infant Swine

Scarborough, John; Daggett, Casey W.; Lodge, Andrew J.; Chai, Paul J.; Williamson, Justin; Jaggers, James; George, Samuel E.; Ungerleider, Ross M.

doi:10.1016/s0022-5223(98)70278-8

Cited by 15 publications

(12 citation statements)

References 22 publications

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“…The measurement 20 mm Hg is close to the normal seen after birth when the pressure falls from 25 to 16 mm Hg by 14 d (1) and 45 mm Hg is a similar pressure to that recorded in hypoxic conditions in young piglets (11). However, the pressures used had little effect on the size or responsiveness of the arteries, whether normal or hypertensive.…”

Section: Hypoxic Pulmonary Resistance Arteriessupporting

confidence: 80%

Relationship between Structural Remodeling and Reactivity in Pulmonary Resistance Arteries from Hypertensive Piglets

et al. 2005

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In neonatal pulmonary hypertension, the pulmonary arteries fail to adapt to extrauterine life and remain thick walled. In a previous study on normal neonatal resistance arteries, perfusion myography and confocal microscopy showed that responses to agonist stimulation were related to wall structure. We hypothesized that in hypertensive resistance pulmonary arteries, an enhanced response to contractile and relaxant agonist stimulation would be associated with an increased wall thickness and abnormal postnatal cytoskeletal remodeling of smooth muscle cells (SMC). Pulmonary arteries (110 -140 m external diameter) from normal piglets and those exposed to chronic hypobaric hypoxia from birth or from 3 d of age were mounted on a perfusion myograph. Lumen diameter and SMC nuclear positions were tracked after addition of KCl, the thromboxane mimetic U46619, and bradykinin. After fixation in situ, SMC dimensions were measured using confocal and electron microscopy. In all hypertensive animals, wall thickness and SMC density were increased and SMC length/width ratio decreased.After hypoxic exposure for 3 d, arteries from animals exposed from birth showed a greater and faster contractile response than controls, but arteries from piglets first exposed at 3 d of age did not, though both showed similar structural appearance. Increase of exposure to 11 d elicited an enhanced response and further cytoskeletal remodeling. All vessels relaxed fully to bradykinin. SMC remodeling and reactivity appear to be influenced by the age at onset and the duration of the hypoxic insult. Rapid structural and functional changes occur in the pulmonary arteries as pulmonary vascular resistance decreases after birth (1). Thick-walled fetal arteries remodel to thin-walled structures within days of birth (2). Using perfusion myography in conjunction with confocal microscopy we found that postnatal elongation of SMC within resistance arteries was associated with a decrease in the speed and extent of vessel constriction in response to agonist stimulation (3).Structural studies on the pulmonary vessels of babies with PPHN and in piglets with experimental PPHN (4 -6) show an increase in pulmonary artery medial thickness and the maturation of SMC in normally nonmuscular precapillary vessels (6). Whereas babies with PPHN appear to have an excessively reactive pulmonary arterial circulation, pharmacological studies on conduit arteries from pulmonary hypertensive piglets showed that there was no increase in the contractile response to potassium chloride (KCl), PGF2␣, or U46619, although the relaxation response to acetylcholine was impaired (7,8). We believed that the resistance pulmonary arteries would show an enhanced response to contractile stimulation, and that the response would be related to the structural abnormalities.In the present study, we hypothesized that the SMC in the thickened wall of resistance arteries from pulmonary hypertensive piglets would show an increase in myofilaments and abnormal cytoskeletal organization in association with an enh...

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Section: Hypoxic Pulmonary Resistance Arteriessupporting

confidence: 80%

Relationship between Structural Remodeling and Reactivity in Pulmonary Resistance Arteries from Hypertensive Piglets

et al. 2005

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“…The same perfusion pressure was used in all preparations, to standardise the procedure. The higher pressure of 45 mm Hg is similar to that found in piglets raised under hypoxic conditions [17]. Also, hypertensive newborn infants can have a transient or sustained increase in pulmonary arterial pressure to a similar level.…”

Section: Discussionsupporting

confidence: 75%

Correlation of Pulmonary Arterial Smooth Muscle Structure and Reactivity during Adaptation to Extrauterine Life

Kelly¹,

Hislop²,

Hall³

et al. 2002

J Vasc Res

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Peripheral pulmonary arteries remodel immediately after birth as pulmonary vascular resistance falls. We hypothesised that there is a link between the response to agonist stimulation and wall structure in early postnatal life. Arteries from fetal, newborn and 14-day-old piglets were mounted on a perfusion myograph. Lumen diameter and smooth muscle cell nuclear positions were recorded after sequential addition of KCl, U46619 and bradykinin. Subsequently, vessels were studied by confocal and transmission electron microscopy. Contractile agonist stimulation caused a greater and faster reduction in lumen diameter in the newborn than at 14 days (p < 0.02) and the distance between cells decreased more in the newborn (p < 0.05). Unstimulated smooth muscle cells changed shape from being rounded in the fetus to fusiform by 14 days, with increasing length/width ratio (p < 0.01). On contraction, length/width ratio decreased most at 14 days (p < 0.01). Extracellular matrix, collagen and elastin, sparse at birth, increased by 14 days. Thus a greater change in lumen diameter in relation to cellular contraction was observed in the newborn than at 14 days and the amount of extracellular matrix within the vessel wall may affect the overall change in lumen diameter.

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“…In our study, it was predictable that there was expression of eNOS in all groups. Whole lung eNOS mRNA was also increased in rats (Shaul et al, 1995) and piglets (Scarborough et al, 1998) with chronic hypoxic pulmonary hypertension. By contrast, McQuillan et al (1994) reported that eNOS expression decreases in pulmonary hypertension and Moreno de Sandino and Hernandez (2003) also demonstrated that hypoxia-induced pulmonary hypertension in broilers is associated with a decrease in endothelial-derived NO expression in pulmonary vessels.…”

Section: Discussionmentioning

confidence: 90%

Evaluation of endothelial and inducible nitric oxide synthase mRNA expression in the lung of broiler chickens with developmental pulmonary hypertension due to cold stress

Teshfam¹,

Brujeni

Hassanpour³

2006

British Poultry Science

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To clarify the effect of cold-induced pulmonary hypertension on endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNA expression in the lung of broiler chickens, semi quantitative reverse transcription-PCR was performed on total RNAs isolated from lungs of the broiler chickens exposed to 5 weeks of cold stress. The eNOS gene was expressed increasingly with the increasing age during the rearing period. Comparing the treatment group with its related control group eNOS was expressed significantly only at d 21. Expression of iNOS mRNA also increased in both control and treatment groups with increasing age until d 28 and then decreased at d 35 and 42. Comparing the treatment group with its control group, iNOS mRNA level was significantly higher at 21 d of age in the cold-exposed chickens. It was concluded that, although cold exposure could significantly increase eNOS and iNOS gene expression, cold-induced pulmonary hypertension is not associated with significant variations of eNOS and iNOS expression in the lungs of broiler chickens.

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The Role Of Endothelial Nitric Oxide Synthase Expression In The Development Of Pulmonary Hypertension In Chronically Hypoxic Infant Swine

Cited by 15 publications

References 22 publications

Relationship between Structural Remodeling and Reactivity in Pulmonary Resistance Arteries from Hypertensive Piglets

Relationship between Structural Remodeling and Reactivity in Pulmonary Resistance Arteries from Hypertensive Piglets

Correlation of Pulmonary Arterial Smooth Muscle Structure and Reactivity during Adaptation to Extrauterine Life

Evaluation of endothelial and inducible nitric oxide synthase mRNA expression in the lung of broiler chickens with developmental pulmonary hypertension due to cold stress

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