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

Kelly, David A.; Hislop, Alison A.; Hall, Susan; Haworth, Sheila G.

doi:10.1159/000048991

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…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).…”

mentioning

confidence: 90%

“…Previous studies have shown that piglets treated in this manner develop pulmonary hypertension, evidenced by right ventricular hypertrophy and an increase in pulmonary arterial smooth muscle (6,8 Functional studies. Perfusion myograph studies were carried out as previously described (3). Briefly peripheral pulmonary arteries immediately proximal to the alveolar region (approx.…”

Section: Origin Of Tissuementioning

confidence: 99%

“…After a washout with PSS, when the vessel returns to baseline, extraluminal U46619 (2 M) was added. The concentration of U46619 was based on previously published dose response studies on pulmonary arteries from normal and hypertensive piglets (3,7). A bolus of 50 L of intraluminal bradykinin (1 M) was then applied, and the vessel allowed to fully relax.…”

Section: Origin Of Tissuementioning

confidence: 99%

“…To relate change in lumen diameter to the response of individual SMC, the position of the fluorescently labeled SMC nuclei was tracked by recording X-Y coordinates for the centre of each nucleus before and after each agonist stimulation, as previously described (3).…”

Section: Origin Of Tissuementioning

confidence: 99%

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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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mentioning

confidence: 90%

Section: Origin Of Tissuementioning

confidence: 99%

Section: Origin Of Tissuementioning

confidence: 99%

Section: Origin Of Tissuementioning

confidence: 99%

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

et al. 2005

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“…Enhanced capacity of growth of fetal and neonatal bovine pulmonary artery adventitial fibroblasts has been demonstrated (33), and more connective tissue was present in piglet pulmonary arteries at 14 d than at birth (34). Connective tissue deposition was also augmented with postnatal age in human pulmonary arteries (35).…”

Section: Nad(p)h-mediated Omentioning

confidence: 99%

Role of Superoxide Anion on Basal and Stimulated Nitric Oxide Activity in Neonatal Piglet Pulmonary Vessels

Villamor¹,

Kessels²,

Fischer

et al. 2003

Pediatr Res

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The superoxide anion (O 2 ⅐Ϫ ) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O 2 ⅐Ϫ is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O 2 ⅐Ϫ levels. SOD (1-300 U/mL) produced endotheliumdependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12-to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12-to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age-or vessel-related differences in O 2 Successful adaptation of the newborn to postnatal conditions requires a dramatic transition of the pulmonary circulation from a high-resistance state in utero to a low-resistance state within minutes after birth. Some infants fail to achieve or sustain this normal decrease in pulmonary vascular resistance, which leads to severe respiratory distress and hypoxemia, referred to as PPHN (1) NO ⅐ , a free radical species produced by a wide variety of cell types, has gained recognition as a key mediator of diverse physiologic and pathologic processes, including the regulation of pulmonary vascular tone and the perinatal adaptation of the lung circulation (1).

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Hypoxic Pulmonary Hypertension of the Newborn

Gao

Raj

2010

Comprehensive Physiology

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Hypoxic pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance and pressure due to vascular remodeling and increased vessel tension secondary to chronic hypoxia during the fetal and newborn period. In comparison to the adult, the pulmonary vasculature of the fetus and the newborn undergoes tremendous developmental changes that increase susceptibility to a hypoxic insult. Substantial evidence indicates that chronic hypoxia alters the production and responsiveness of various vasoactive agents such as endothelium-derived nitric oxide, endothelin-1, prostanoids, platelet-activating factor, and reactive oxygen species, resulting in sustained vasoconstriction and vascular remodeling. These changes occur in most cell types within the vascular wall, particularly endothelial and smooth muscle cells. At the cellular level, suppressed nitric oxide-cGMP signaling and augmented RhoA-Rho kinase signaling appear to be critical to the development of hypoxic pulmonary hypertension of the newborn.

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

Cited by 11 publications

References 29 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

Role of Superoxide Anion on Basal and Stimulated Nitric Oxide Activity in Neonatal Piglet Pulmonary Vessels

Hypoxic Pulmonary Hypertension of the Newborn

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