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

Abstract

Prenatal hypoxia, a common pregnancy complication, leads to cardiac and 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-threatening 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 15 to 21 (term = 22 days; n = 9 or 10/group). Carotid arteries were isolated from the 4-mo-old male and female offspring. Vasoconstrictor and vasodilatory properties were assessed by wire myography, and biomechanical properties (myogenic tone, circumferential stress, and strain) were assessed 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 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 exposure to prenatal hypoxia affects the carotid arteries of the adult offspring in a sex-specific manner, which may impact the blood flow regulation to the brain.NEW & NOTEWORTHY Little is known about the (long-lasting) impact of pregnancy complications on offspring carotid artery function. We showed that, in adult male offspring, prenatal hypoxia decreased carotid artery myogenic tone and stiffness and changed collagen and elastin densities, whereas in females, prenatal hypoxia increased stiffness. These findings contribute to understanding sex-specific differences of adult offspring exposed to a suboptimal in utero environment on the carotid arteries, an important/easily accessible vascular bed for patient disease evaluation.