Augmented vasoreactivity in adult life associated with perinatal vascular insult

Sartori, Cláudio; Allemann, Yves; Trueb, Lionel; Delabays, Alain; Nicod, Pascal; Scherrer, Urs

doi:10.1016/s0140-6736(98)08352-4

Cited by 144 publications

(93 citation statements)

References 9 publications

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“…43 One factor influencing P pa during adulthood is perinatal hypoxia, as shown by human and experimental animal studies in which greater hypoxia in utero or during the neonatal period increased the reactivity of the pulmonary vasculature to hypoxia later in life. 44,45 Perinatal hypoxia is greater at high than at low altitudes, as demonstrated by the known reduction in birth weight resulting from slowed fetal growth, 46 Doppler indices of fetal hypoxia, 47 and lower postnatal arterial O 2 saturations (SaO 2 's). 48 Perinatal hypoxia also varies among populations; the altitude-associated reductions in fetal growth are only half (45%) as great in Tibetans or Andeans as in Han or Europeans residing at the same altitudes (Fig.…”

mentioning

confidence: 99%

Neonatal Oxygenation, Pulmonary Hypertension, and Evolutionary Adaptation to High Altitude (2013 Grover Conference series)

Niermeyer

Andrade-M²,

Vargas

et al. 2015

Pulm. circ.

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Andeans and Tibetans have less altitude reduction in birth weight than do shorter-resident groups, but only Tibetans are protected from pulmonary hypertension and chronic mountain sickness (CMS). We hypothesized that differences in neonatal oxygenation were involved, with arterial O 2 saturation (SaO 2 ) being highest in Tibetans, intermediate in Andeans, and lowest in Han or Europeans, and that improved oxygenation in Andeans relative to Europeans was accompanied by a greater postnatal decline in systolic pulmonary arterial pressures (P pa sys ). We studied 41 healthy (36 Andeans, 5 Europeans) and 9 sick infants at 3,600 m in Bolivia. The SaO 2 in healthy babies was highest at 6-24 hours of postnatal age and then declined, whereas sick babies showed the opposite pattern. Compared to that of 30 Tibetan or Han infants studied previously at 3,600 m, SaO 2 was higher in Tibetans than in Han or Andeans during wakefulness and active or quiet sleep. Tibetans, as well as Andeans, had higher values than Han while feeding. The SaO 2 's of healthy Andeans and Europeans were similar and, like those of Tibetans, remained at 85% or above, whereas Han values dipped below 70%. Andean and European P pa sys values were above sea-level norms and higher in sick than in healthy babies, but right heart pressure decreased across 4-6 months in all groups. We concluded that Tibetans had better neonatal oxygenation than Andeans at 3,600 m but that, counter to our hypothesis, neither was SaO 2 higher nor P pa lower in Andean than in European infants. Further, longitudinal studies in these 4 groups are warranted to determine whether neonatal oxygenation influences susceptibility to high-altitude pulmonary hypertension and CMS later in life.Keywords: Andean, cardiopulmonary transition, Ethiopian, European, genetic adaptation, Han, hypoxia, Tibet. Studies at high altitude have long provided a useful model for persons interested in the pulmonary circulation. [1][2][3][4] While pulmonary arterial pressures (P pa 's) are generally elevated at high altitude, there is considerable population variation in both P pa and pulmonary circulation-related disorders such as chronic mountain sickness (CMS; Fig. 1A) 11,36 and subacute infantile mountain sickness. 37 Specifically, directly measured P pa and hypoxic pulmonary vasoconstrictor responses are lowest in Tibetans, intermediate in Andeans, and highest in European-derived residents of Colorado (Fig. 1B). Recent estimates using echocardiography also suggest intermediate values in Ethiopians. 15 While multiple factors contribute to the etiology of CMS and no well-controlled comparative epidemiological studies exist, a reduced prevalence among Tibetans is consistent with the lower hemoglobin levels seen in Tibetans, relative to Andeans, in multiple reports. [38][39][40] Tibetans are also protected, relative to Han, from subacute infantile mountain sickness, a syndrome characterized by severe pulmonary hypertension in 4-6-month-old infants that has also been reported in European-derived popul...

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confidence: 99%

Neonatal Oxygenation, Pulmonary Hypertension, and Evolutionary Adaptation to High Altitude (2013 Grover Conference series)

Niermeyer

Andrade-M²,

Vargas

et al. 2015

Pulm. circ.

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“…Under conditions of generalized hypoxia, however, total pulmonary vascular resistance rises with subsequent increase of right heart load (1-3). Chronic hypoxia, as occurring in ventilatory disorders induces chronic pulmonary hypertension, pulmonary vascular remodeling, and cor pulmonale (4). The underlying oxygen sensing and signal transduction mechanisms of the acute and chronic vascular responses are largely unknown.…”

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confidence: 99%

Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange

Weißmann

Dietrich

Fuchs

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

271

285

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Regional alveolar hypoxia causes local vasoconstriction in the lung, shifting blood flow from hypoxic to normoxic areas, thereby maintaining gas exchange. This mechanism is known as hypoxic pulmonary vasoconstriction (HPV). Disturbances in HPV can cause life-threatening hypoxemia whereas chronic hypoxia triggers lung vascular remodeling and pulmonary hypertension. The signaling cascade of this vitally important mechanism is still unresolved. Using transient receptor potential channel 6 (TRPC6)-deficient mice, we show that this channel is a key regulator of acute HPV as this regulatory mechanism was absent in TRPC6 ؊/؊ mice whereas the pulmonary vasoconstrictor response to the thromboxane mimetic U46619 was unchanged. Accordingly, induction of regional hypoventilation resulted in severe arterial hypoxemia in TRPC6 ؊/؊ but not in WT mice. This effect was mirrored by a lack of hypoxiainduced cation influx and currents in smooth-muscle cells from precapillary pulmonary arteries (PASMC) of TRPC6 ؊/؊ mice. In both WT and TRPC6 ؊/؊ PASMC hypoxia caused diacylglycerol (DAG) accumulation. DAG seems to exert its action via TRPC6, as DAG kinase inhibition provoked a cation influx only in WT but not in TRPC6 ؊/؊ PASMC. Notably, chronic hypoxia-induced pulmonary hypertension was independent of TRPC6 activity. We conclude that TRPC6 plays a unique and indispensable role in acute hypoxic pulmonary vasoconstriction. Manipulation of TRPC6 function may thus offer a therapeutic strategy for the control of pulmonary hemodynamics and gas exchange.hypoxia-induced diacylglycerol accumulation ͉ precapillary pulmonary arterial smooth-muscle cells ͉ pulmonary hypertension ͉ transient receptor potential channel 6-deficient mouse model ͉ arterial hypoxemia A cute regional hypoxic pulmonary vasoconstriction (HPV) is necessary to maintain optimized gas exchange by directing blood flow from poorly ventilated to well ventilated areas of the lung. Under conditions of generalized hypoxia, however, total pulmonary vascular resistance rises with subsequent increase of right heart load (1-3). Chronic hypoxia, as occurring in ventilatory disorders induces chronic pulmonary hypertension, pulmonary vascular remodeling, and cor pulmonale (4). The underlying oxygen sensing and signal transduction mechanisms of the acute and chronic vascular responses are largely unknown. A rise of intracellular calcium ([Ca 2ϩ ] i ) in pulmonary artery smooth-muscle cells (SMCs) has been suggested to be the key event in these processes (5-8). However, the question how [Ca 2ϩ ] i is regulated has not yet been resolved. Among others, transient receptor potential (TRP) channels are regulators of [Ca 2ϩ ] i . The TRP protein superfamily consists of a diverse group of nonselective cation channels involved in many basic cellular processes (9). Whereas members of the TRPV and TRPM subfamilies have emerged as versatile cellular sensors, the functional importance of the seven members (TRPC1 to -7) of the TRPC (transient receptor potential cation channel subfamily C) subfamily...

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“…It is postulated that the reduced DL CO at rest observed in the studies may suggest the prolonged influence of antenatal programming (Narang et al, 2009). Certainly, pulmonary circulatory abnormalities have been observed in adult subjects with a transient history of lung injury secondary to persistent fetal circulation in the neonatal period (Sartori et al, 1999). These subjects, with normal pulmonary artery pressure at rest, demonstrated an exaggerated pulmonary artery pressure increase at high altitude compared with controls (Sartori et al, 1999).…”

Section: Summary and Implicationsmentioning

confidence: 87%

Preterm Birth and Long-Term Pulmonary Function

Narang¹,

Al-Naimi²

2012

Preterm Birth - Mother and Child

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Augmented vasoreactivity in adult life associated with perinatal vascular insult

Cited by 144 publications

References 9 publications

Neonatal Oxygenation, Pulmonary Hypertension, and Evolutionary Adaptation to High Altitude (2013 Grover Conference series)

Neonatal Oxygenation, Pulmonary Hypertension, and Evolutionary Adaptation to High Altitude (2013 Grover Conference series)

Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange

Preterm Birth and Long-Term Pulmonary Function

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