Regional heterogeneity of vascular reactivity along the aorta: consideration of sex as a biological variable

In mammals, the aorta develops from fusion between multiple embryonic blood vessels, to extend as a single blood vessel from the heart to the abdominal cavity. Due to the heterogenic origins of this vessel, we hypothesized that there are distinct regional differences in vascular function in adults. Indeed, in pathophysiological conditions, such as aortic aneurysm, aneurysms are more likely to develop closer to the heart compared to the caudal end of the aorta. There are also known sex differences in the development of aortic aneurysms, indicating a need to study the regional differences in vasomotor responses along the aorta. Here, we characterize vasocontractile, vasodilatory, and structural components from four distinct segments of the aorta (ascending, descending, lower thoracic, and infrarenal) in male and female C57BL/6J mice at 15-20 weeks of age. Isolated aortic segments were mounted using 40 µm stainless steel wires on a 4-channel wire myograph (Danish Myo Technology) containing physiological salt solution. Once warmed to ~37°C, aortic segments were normalized and isometric force measurements were recorded. Aortic segments were treated with exogenous pharmacological agents (agonists and/or antagonists) for concentration response curves or electrical field stimulation (EFS) to stimulate endogenous neurotransmitter release from sympathetic perivascular nerves. Overall, we observed distinct functional profiles and length-tension relationships for each aortic segment, including differences between vessels from male and female mice. With exception of the infrarenal aortic segment, we observed enhanced vasoconstriction to the alpha-1 adrenoceptor agonist, phenylephrine, in females compared to males. Additionally, the infrarenal aorta was uniquely resistant to KCl-mediated vasoconstriction relative to the other segments. Nonspecific adrenoceptor stimulation by norepinephrine showed regional differences in vasoconstriction, while the sex differences were less apparent as compared to phenylephrine. Although regional differences in vasoconstriction were observed during stimulation of sympathetic nerves by EFS, sex differences were more subtle. Thus, sex as a biological variable may differ when comparing endogenous neurovascular transmission to exogenous addition of pharmacological agents in different aortic segments. Finally, endothelial-dependent vasodilation differed throughout aortic regions, while smooth muscle-dependent vasodilation was consistent throughout. Altogether, these data highlight the importance of sex as a biological variable in vascular reactivity along the aorta, and demonstrates that no two regions of the aorta are the same. National Institutes of Health Grant R01HL155618 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.