Background: Chronic exercise has been linked to positive effects on cognitive function and brain health. The aim of our study was to investigate how exercise affects cerebral resistance artery morphology, with an underlying focus on potential sex differences. Methods: Wistar rats were divided into male exercising (M.Ex; n = 6), female exercising (F.Ex; n = 5), male sedentary (M.Sed; n = 5), and female sedentary (F.Sed; n = 5) groups. After a 12-week swimming program, histological examinations of the intracerebral and pial arterioles were performed. SMA-DAB (smooth muscle actin) and resorcin-fuchsin (elastica) stained brain coronal sections were used for quantitative colorimetric analysis. Results: Investigating the effect of exercise, we found that in both pial and intracerebral arterioles, the elastic fiber density increased in both female and male exercising animals compared to the sedentary groups (p < 0.05 (M.Sed vs. M.Ex); p < 0.0001 (F.Sed vs. F.Ex)). As sex differences, we found that in female animals’ pial arterioles, the density of elastic fiber was increased compared to the male exercising group (p < 0.001 (M.Ex vs. F.Ex)). In pial arterioles, the smooth muscle density was higher in the male sedentary animals (p < 0.01 (M.Sed vs. F.Sed)); in intracerebral arterioles, the smooth muscle density increased with exercise in the male animals as well (p < 0.0001 (M.Ex vs. F.Ex)). Conclusions: Our results demonstrate that the increase in vascular elasticity is more pronounced overall in female animals.

Chronic exercise induces functional adaptations in skeletal muscle microcirculation, but whether these are accompanied by sex-specific histological remodeling of arterioles remains unclear. This study examined gracilis muscle arterioles in trained (Ex) and sedentary (Se) female (F) and male (M) Wistar rats after a 12-week intensive swimming program (Mex = 6, FEx = 6; MSed = 6, FSed = 5). Histological remodeling was assessed by quantitative colorimetry analysis of resorcin-fuchsin (elastica; n = 661) and SMA-DAB (smooth muscle actin; n = 692) staining, focusing on elastic fiber density, internal elastic lamina (IEL) characteristics, and smooth muscle density in intramuscular and intermuscular vessels. Elastic fiber density and IEL thickness were generally greater in female animals than in males (p < 0.05). IEL staining intensity showed significant effects of sex (p = 0.043), exercise (p = 0.021), and a significant sex-by-exercise interaction (p = 0.037), with exercised females exhibiting the highest IEL staining intensity. Smooth muscle density did not differ significantly by sex or training status, although it was higher in intermuscular than intramuscular arterioles (p < 0.001), and increased with vessel diameter primarily in the intermuscular group. These findings demonstrate exercise-induced, sex-specific histological remodeling of skeletal muscle arterioles, primarily affecting elastic components, with more pronounced elastic adaptation in females.