The role of nitric oxide in the cardiopulmonary response to hypoxia in high- and lowland newborn llamas

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 NO in the cardiopulmonary responses to acute hypoxia in high- and low-land 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 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 α-actin expression.

High- compared to low-land newborn llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, since NO blockade reverted the effect and the pulmonary arterial dilator 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 or 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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