Regional heterogeneity and sex differences along the mouse aorta

The aorta varies in structural and biomechanical properties along its length, however, the influence of these properties on aortic pathology is poorly understood. By understanding vascular reactivity profiles along the aorta, we can target treatment with regional specificity. Here, we characterize vascular function in four distinct segments of the aorta (ascending, proximal thoracic, distal thoracic, and infrarenal) in C57BL/6J mice. Aortic segments were isolated and assessed functionally via wire myography, where segments were treated with exogenous pharmacological agents or electrical field stimulation (EFS) to evaluate changes in isometric force measurement. Overall, we observed distinct functional profiles and length-tension relationships for each aortic segment, including sex differences. With exception of the infrarenal aortic segment, we observed enhanced vasoconstriction in females to the α1-adrenergic receptor agonist, phenylephrine. The infrarenal aorta was uniquely resistant to KCl-mediated vasoconstriction relative to the other segments regardless of sex. Nonspecific adrenergic receptor stimulation by norepinephrine showed regional differences in vasoconstriction, while the sex differences were less apparent compared to phenylephrine. Although regional differences in vasoconstriction were observed during sympathetic nerve stimulation by EFS, sex differences were not seen. Our findings suggest that sex as a variable differs along the aorta when comparing endogenous neurovascular transmission to exogenous pharmacological agents. Interestingly, we found that the magnitude of endothelial-dependent vasodilation varied by aortic region, while smooth muscle-dependent vasodilation was consistent across all segments. These data highlight the importance of sex as a biological variable in understanding vascular reactivity along the aorta and demonstrate that aortic function is region specific.