Exposure to prenatal hypoxia impairs the function and structure of the carotid arteries in the adult offspring.

Abstract

Prenatal hypoxia, a common pregnancy complication, can lead to vascular dysfunction, thereby increasing the risk of cardiovascular disease in the adult offspring. Carotid arteries are responsible for the majority of the blood flow to the brain/head, and carotid artery dysfunction is associated with life-threating cardiovascular events, such as stroke. However, whether prenatal hypoxia exposure impacts the function of the carotid arteries in the adult offspring is not known. We hypothesize that prenatal hypoxia impairs carotid artery function in the adult male and female offspring. Sprague Dawley rats were exposed to normoxia (21% O₂) or hypoxia (11% O₂) from gestational day (GD) 15 to 21 (term=22 days; n=9-11/group). Carotid arteries were isolated from the 4-month-old adult male and female offspring. Vasoconstrictor and vasodilatory properties were assessed by wire myography, and biomechanical properties (myogenic tone, circumferential stress and strain) by pressure myography. Collagen deposition (Masson's trichrome stain) and elastin density (Verhoeff stain) were measured in carotid artery cryosections. Prenatal hypoxia did not impact vasoconstriction or vasorelaxation responses in carotid arteries from both offspring. However, in males, prenatal hypoxia reduced carotid artery myogenic tone development and increased circumferential strain, which coincided with a lower collagen deposition and higher elastin density. In females, prenatal hypoxia tended to lower carotid artery circumferential strain (i.e., increased stiffness), without differences in myogenic tone or collagen/elastin density. Altogether, these data show that prenatal hypoxia exposure affects the carotid arteries of the adult offspring in a sex-specific manner, which may impact the blood flow regulation to the brain.