Sex Differences in Aortic Remodeling During Blood Pressure Reduction Following Gradual Hypertension Development in Spontaneously Hypertensive Rats

BackgroundCardiovascular disease risk is higher in men than in women. Although sex differences in aortic wall adaptation following antihypertensive treatment have been reported in acute hypertension models, the response after gradually developing hypertension, which mimics human essential hypertension, remains unclear. This study investigated sex differences in aortic wall adaptation following acute blood pressure reduction after gradually developing hypertension. MethodSeventeen-week-old spontaneously hypertensive rats (SHRs) were assigned to the Hypertensive group or the antihypertensive (Reversal) group (N = 5/sex each). The Reversal group received the antihypertensive drug captopril for 4 weeks to maintain systolic blood pressure below 130 mmHg. Age-matched Wistar Kyoto rats (N = 3/sex) served as normotensive (Normal) group. After the experimental period, arterial wall thickness, circumferential wall stress, smooth muscle cell phenotype, and histological changes were evaluated. ResultsAntihypertensive treatment significantly reduced systolic blood pressure in both sexes. Both male and female SHRs exhibited elevated circumferential wall stress during the gradual development of hypertension. In females, antihypertensive treatment significantly reduced medial thickness compared with the Hypertensive group, whereas males showed no reduction. Circumferential wall stress in female Reversal group did not differ significantly from either the Hypertensive or Normal group, whereas males exhibited a significant reduction in circumferential wall stress compared with the Hypertensive group. Furthermore, the reduced collagen area fraction in the Hypertensive group returned to the normotensive levels only in females following antihypertensive treatment. ConclusionThese findings indicate that vascular remodeling induced by gradually developing hypertension is more effectively reversed by antihypertensive treatment in females than in males.