Impact of ageing on the deleterious effects caused to the large arteries by intermittent hypoxia in mice

Abstract

The Obstructive Sleep Apnea Syndrome (OSAS) features intermittent upper airway occlusions during sleep, leading to intermittent hypoxia (IH) and blood oxygen desaturation. OSAS affects up to 38% of the population (up to 49% in the elderly), and mainly concerns males. OSAS has severe detrimental effects on the cardiovascular system, such as hypertension and increased risk of cardiac infarct. In this study, we assessed the impact of ageing on the IH-induced deleterious effects in the aorta of aged and adult (24 and 6 months old) mice, male and female, exposed to IH (8 hours/day, 1 minute cycles, alternating 30 s at 21% O 2 and 30 s at 5% O 2 in 6 months old and 10% O 2 in 24 months old mice) or normoxia (21% O 2 ) for 14 days. Using the techniques of pressure-arteriography and two-photon microscopy, we have shown that both IH and age affect the mechanical and structural properties of the aorta, with gender-dependent characteristics. IH and ageing induce disruptions in and disorganization of the aortic elastic fibres, although differently in males and females. While IH and age increase the aorta diameter in both gender, they generally decrease aortic thickness and increase rigidity in females only, while, in males, the impacts of hypoxia are different as a function of age. The aortic reactivity is also differentially impacted by IH as a function of gender and age, with a higher acetylcholine-induced vasodilation in IH aged females and a higher phenylephrine(PE)-induced constriction in IH adult males. The latter fits with the higher PE-induced increase in intracellular calcium level that we measured in cultured vascular smooth muscle cells from IH adult males. These results emphasize on the fact that OSAS has different impacts on the mouse cardiovascular system, depending on both age and gender. These new findings should be verified in patients, in order to optimize the therapeutic strategy for each age and gender groups.