Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

- In the rat, hypobaric hypoxia (7315 m) for 24 h increased sympathetic nerve activity, systemic and pulmonary artery pressures, and lung microvascular permeability.
- Lesioning of and muscimol infusion into posterior hypothalamus attenuated these responses.
- Nitric oxide infusion had no effects.

To investigate the role of posterior hypothalamus and central neurotransmitters in the pulmonary edema due to hypobaric hypoxia, rats were placed in a high altitude simulation chamber (barometric pressure-294.4 mmHg) for 24 h. Exposure to hypobaric hypoxia resulted in increases in mean arterial blood pressure, renal sympathetic nerve activity, right ventricular systolic pressure, lung wet to dry weight ratio and Evans blue dye leakage. There was a significant attenuation in these responses to hypobaric hypoxia (a) after lesioning posterior hypothalamus and (b) after chronic infusion of GABAA receptor agonist muscimol into posterior hypothalamus. No such attenuation was evident with the chronic infusion of the nitric oxide donor SNAP into the posterior hypothalamus. It is concluded that in hypobaric hypoxia, there is over-activity of posterior hypothalamic neurons probably due to a local decrease in GABA-ergic inhibition which increases the sympathetic drive causing pulmonary hypertension and edema.