An animal model of the relationship between systemic hypertension and repetitive episodic hypoxia as seen in sleep apnoea

SUMMARY  Multiple factors may be responsible for acute and chronic blood pressure changes during obstructive sleep apnoea. A popular hypothesis is that recurrent episodic hypoxia stimulates chemoreceptors which, in turn, cause sympathetically mediated vasoconstriction and perhaps long‐term vascular remodelling. Disruption of sleep architecture secondary to frequent arousals may also cause chronic stress which may contribute to diurnal hypertension. A less likely factor elevating blood pressure is the effect of abrupt intra‐thoracic pressure changes on venous return and cardiac output. The rat responds to chronic, recurrent episodic hypocapnic hypoxia (12‐s bursts of nitrogen followed by air into Plexiglas chambers, every 30 s, 7h d ‐1 , 2–4% nadir ambient oxygen) with sustained increase in diurnal blood pressure (10–14 mmHg). Subsequent studies reveal that carotid sinus nerve section (chemodener‐vation) and chemically induced peripheral sympathetic denervation with the neurotoxin 6‐OH dopamine both eliminate this blood pressure‐elevating effect of chronic episodic hypoxaemia. Using this model, Sprague‐Dawley rats have been challenged with both eucapnic hypoxia and asphyxia and failed to show an additional blood pressure elevation above that caused by hypoxia (hypocapnic) alone. It appears that hypocapnic hypoxia creates a maximal stimulus to the sympathetic nervous system to which the addition of hypercarbia does not increase the blood pressure response. An alternative explanation is that the rat has protective mechanisms that limit the diurnal blood pressure response from further increase.