Graton Murilo E, de Oliveira Amanda A, Neupane Aryan, Quon Anita, Kirschenman Raven, Spaans Floor, Davidge Sandra T
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
Am J Physiol Heart Circ Physiol. 2025 Mar 1;328(3):H518-H525. doi: 10.1152/ajpheart.00859.2024. Epub 2025 Jan 31.
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% O) or hypoxia (11% O) from gestational day 15 to 21 (term = 22 days; = 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. 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.
产前缺氧是一种常见的妊娠并发症，会导致心脏和血管功能障碍，从而增加成年后代患心血管疾病的风险。颈动脉负责向大脑/头部输送大部分血液，颈动脉功能障碍与中风等危及生命的心血管事件相关。然而，产前缺氧暴露是否会影响成年后代的颈动脉功能尚不清楚。我们假设产前缺氧会损害成年雄性和雌性后代的颈动脉功能。将斯普拉格-道利大鼠从妊娠第15天至21天暴露于常氧（21%氧气）或缺氧（11%氧气）环境（孕期=22天；每组n = 9或10）。从4月龄的雄性和雌性后代中分离出颈动脉。通过线肌张力测定法评估血管收缩和舒张特性，通过压力肌张力测定法评估生物力学特性（肌源性张力、周向应力和应变）。在颈动脉冰冻切片中测量胶原蛋白沉积（Masson三色染色）和弹性蛋白密度（Verhoeff染色）。产前缺氧并未影响两代后代颈动脉的血管收缩或血管舒张反应。然而，在雄性后代中，产前缺氧降低了颈动脉肌源性张力的发展并增加了周向应变，这与较低的胶原蛋白沉积和较高的弹性蛋白密度相一致。在雌性后代中，产前缺氧倾向于降低颈动脉周向应变（即增加硬度），而肌源性张力或胶原蛋白/弹性蛋白密度没有差异。总之，这些数据表明，产前缺氧暴露以性别特异性方式影响成年后代的颈动脉，这可能会影响大脑的血流调节。关于妊娠并发症对后代颈动脉功能的（长期）影响知之甚少。我们表明，在成年雄性后代中，产前缺氧降低了颈动脉肌源性张力和硬度，并改变了胶原蛋白和弹性蛋白密度，而在雌性后代中，产前缺氧增加了硬度。这些发现有助于理解暴露于子宫内不良环境的成年后代在颈动脉方面的性别特异性差异，颈动脉是用于患者疾病评估的重要/易于获取的血管床。
