Abstract

Introduction: There are known sex differences in peripheral artery disease (PAD) symptom presentation with women manifesting atypical symptoms and a higher vascular burden. Women are also more prone to periprocedural complications possibly due to sex-specific endothelial dysfunction and microvascular impairment. There is a critical need to understand sex specific differences in microvascular function to improve outcomes for women with PAD. Hypothesis: Lower limb arteriolar flow induced dilation (FID) will be significantly reduced in women, compared to men. Methods: Combined muscle and fat tissue were obtained from the affected leg in patients undergoing revascularization due to PAD. Arterioles were dissected, cannulated, and suspended in a physiological chamber at a stable intraluminal pressure. FID was assessed at increasing intraluminal pressure gradients. A subsample of vessels underwent arteriolar dilation with ACh with and without L-NAME, and SNP. Results: We quantified arteriolar FID in 24 arterioles (7=not viable) from 18 patients undergoing revascularization due to PAD (age 60.2 + 7.4, 44%=F, 61%=Black). Heterogeneity was observed in FID with significantly reduced response observed in women. FID in women at 60 cmH 2 O was 24.7 + 20.5%, compared to 52.6 + 28.0% in men, p=.05, and AUC was 69.0 + 66.8 in women, compared to 147.6 + 82.0 in men (p=.07). Findings were similar in both muscle and adipose arterioles. Vessels treated with Ach responded similar to FID. Vessels treated with L-NAME and SNP showed variable blunted response. Conclusions: Women had more impairment in arteriolar function compared to men, providing insight into sex dimorphism in the PAD population. Findings indicated that FID in arterioles is mostly nitric oxide dependent, although patient and sex specific changes in vascular smooth muscle signaling/function are present. This study support the need to develop microvascular and sex specific interventions for patients with PAD.

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