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Anibal J Llanos - One of the best experts on this subject based on the ideXlab platform.
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perinatal cardiopulmonary adaptation to the thin air of the alto andino by a native altiplano dweller the Llama
Journal of Applied Physiology, 2020Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Anibal J LlanosAbstract:Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the Llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the Llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the Llama fetus to protect its brain against hypoxic damage. During hypoxia, in the Llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn Llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland Llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn Llama pulmonary vasculature. These three striking physiological adaptations of the Llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.
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the role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn Llamas
The Journal of Physiology, 2018Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Marcela Diaz, Julian T. Parer, Sebastian Quezada, Ismael Hernandez, Anibal J LlanosAbstract:Key points Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the Llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn Llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. We show that high- compared to lowland newborn Llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland Llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn Llama. Abstract Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. The cardiopulmonary function of newborn Llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn Llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude Llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn Llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
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fetal and postnatal pulmonary circulation in the alto andino
Placenta, 2011Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Anibal J Llanos, Victor M Pulgar, Maria Seronferre, Marcela DiazAbstract:Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the Llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal Llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the Llama fetus compared to the sheep fetus. Altogether these data show that the fetal Llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal Llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and Llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in Llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal Llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult Llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the Llama. The Llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
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Fetal and maternal blood oxygen affinity: a comparative study in Llamas and sheep.
Comparative biochemistry and physiology. Part A Physiology, 1996Co-Authors: Fernando A. Moraga, Raquel A. Riquelme, Carlos Monge, Anibal J LlanosAbstract:We compared blood oxygen affinity (P50) and hemoglobin concentration among fetal and maternal Llamas and sheep, as respective examples of species native to high and low altitudes. P50, hemoglobin concentration and blood oxygen content were determined at sea level in 16 pregnant Llamas, 6 pregnant sheep and their respective fetuses. P50 was similar in fetal Llamas and sheep, but maternal Llamas had higher blood oxygen affinity than maternal sheep. As a consequence, the P50 difference between mother and fetus was less in Llamas than in sheep. Fetal Llamas had higher hemoglobin concentrations than fetal sheep. In contrast, the maternal hemoglobin concentrations were similar. The blood oxygen content was higher in fetal and maternal Llamas than in fetal and maternal sheep. We conclude that the Llama, a species native to the altiplano, has a higher blood oxygen content than the sheep, as determined in the fetus by a high hemoglobin concentration and in the mother by a low P50.
Roberto V Reyes - One of the best experts on this subject based on the ideXlab platform.
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perinatal cardiopulmonary adaptation to the thin air of the alto andino by a native altiplano dweller the Llama
Journal of Applied Physiology, 2020Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Anibal J LlanosAbstract:Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the Llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the Llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the Llama fetus to protect its brain against hypoxic damage. During hypoxia, in the Llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn Llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland Llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn Llama pulmonary vasculature. These three striking physiological adaptations of the Llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.
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the role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn Llamas
The Journal of Physiology, 2018Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Marcela Diaz, Julian T. Parer, Sebastian Quezada, Ismael Hernandez, Anibal J LlanosAbstract:Key points Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the Llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn Llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. We show that high- compared to lowland newborn Llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland Llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn Llama. Abstract Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. The cardiopulmonary function of newborn Llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn Llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude Llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn Llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
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fetal and postnatal pulmonary circulation in the alto andino
Placenta, 2011Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Anibal J Llanos, Victor M Pulgar, Maria Seronferre, Marcela DiazAbstract:Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the Llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal Llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the Llama fetus compared to the sheep fetus. Altogether these data show that the fetal Llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal Llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and Llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in Llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal Llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult Llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the Llama. The Llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
Emilio A Herrera - One of the best experts on this subject based on the ideXlab platform.
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perinatal cardiopulmonary adaptation to the thin air of the alto andino by a native altiplano dweller the Llama
Journal of Applied Physiology, 2020Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Anibal J LlanosAbstract:Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the Llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the Llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the Llama fetus to protect its brain against hypoxic damage. During hypoxia, in the Llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn Llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland Llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn Llama pulmonary vasculature. These three striking physiological adaptations of the Llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.
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the role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn Llamas
The Journal of Physiology, 2018Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Marcela Diaz, Julian T. Parer, Sebastian Quezada, Ismael Hernandez, Anibal J LlanosAbstract:Key points Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the Llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn Llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. We show that high- compared to lowland newborn Llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland Llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn Llama. Abstract Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. The cardiopulmonary function of newborn Llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn Llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude Llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn Llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
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fetal and postnatal pulmonary circulation in the alto andino
Placenta, 2011Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Anibal J Llanos, Victor M Pulgar, Maria Seronferre, Marcela DiazAbstract:Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the Llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal Llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the Llama fetus compared to the sheep fetus. Altogether these data show that the fetal Llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal Llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and Llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in Llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal Llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult Llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the Llama. The Llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
German Ebensperger - One of the best experts on this subject based on the ideXlab platform.
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perinatal cardiopulmonary adaptation to the thin air of the alto andino by a native altiplano dweller the Llama
Journal of Applied Physiology, 2020Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Anibal J LlanosAbstract:Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the Llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the Llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the Llama fetus to protect its brain against hypoxic damage. During hypoxia, in the Llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn Llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland Llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn Llama pulmonary vasculature. These three striking physiological adaptations of the Llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.
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the role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn Llamas
The Journal of Physiology, 2018Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Marcela Diaz, Julian T. Parer, Sebastian Quezada, Ismael Hernandez, Anibal J LlanosAbstract:Key points Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the Llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn Llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. We show that high- compared to lowland newborn Llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland Llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn Llama. Abstract Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. The cardiopulmonary function of newborn Llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn Llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude Llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn Llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
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fetal and postnatal pulmonary circulation in the alto andino
Placenta, 2011Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Anibal J Llanos, Victor M Pulgar, Maria Seronferre, Marcela DiazAbstract:Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the Llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal Llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the Llama fetus compared to the sheep fetus. Altogether these data show that the fetal Llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal Llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and Llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in Llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal Llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult Llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the Llama. The Llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
Marcela Diaz - One of the best experts on this subject based on the ideXlab platform.
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the role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn Llamas
The Journal of Physiology, 2018Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Emilia M Sanhueza, Dino A Giussani, Marcela Diaz, Julian T. Parer, Sebastian Quezada, Ismael Hernandez, Anibal J LlanosAbstract:Key points Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the Llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn Llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. We show that high- compared to lowland newborn Llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland Llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn Llama. Abstract Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn Llamas. The cardiopulmonary function of newborn Llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn Llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude Llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn Llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.
-
fetal and postnatal pulmonary circulation in the alto andino
Placenta, 2011Co-Authors: Roberto V Reyes, Emilio A Herrera, German Ebensperger, Anibal J Llanos, Victor M Pulgar, Maria Seronferre, Marcela DiazAbstract:Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the Llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal Llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the Llama fetus compared to the sheep fetus. Altogether these data show that the fetal Llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal Llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and Llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in Llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal Llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult Llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the Llama. The Llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
