Changes in vascular elasticity due to the consumption of high salt: Sex differences

Arterial stiffness and alteration in vascular biomechanics play pivotal roles in circulatory dysfunction. Furthermore, the pharmacological responses of vasoactive agents on biomechanics are less defined in salt-induced hypertension in males versus females. Therefore, the studies undertaken for this thesis investigated the changes in the structure and biomechanics of small resistance arteries from salt-sensitive male and female Dahl rats fed regular and high salt diets for 6-7 weeks (n=6-8/group). Third-order mesenteric arteries were used, and the effects of pharmacological agents on biomechanics were assessed using pressure myography. Rats on a high salt diet (H) developed hypertension with elevated pulse wave velocity compared to rats on a regular diet (R). Morphometric assessment of the vessel wall indicated the possible development of hypertrophy with a significant increase in collagen and smooth muscle cell areas in males (H) compared (R) and the corresponding females. While no significant differences in composite Young's modulus (CYM) were found between groups, vasoconstriction (phenylephrine, 0.3 μM) resulted in significantly higher CYM in males (H) than (R) and the corresponding females on a high salt diet or regular diet. In contrast, vasodilation (sodium nitroprusside, 0.3 μM) significantly reduced CYM in the male groups (H) compared to the corresponding values in females (H). Inhibition of endothelial cell function using (L-NAME 0.3 μM, Ouabain 100 μM, and BaCl2 100 μM) or by denudation significantly increased CYM in male (R), female (R) and female (H) but not in male (H). Immunohistochemical assessment of biomechanical markers of arterial stiffness revealed significant sex differences, which may contribute to differential mechanisms of arterial stiffness in males versus females. Assessment of sex-specific contributions of Piezo 1 channels in vascular biomechanics indicated a differential expression of Piezo 1 mechanosensitive ion channels. In intact tissue, Piezo 1 antagonist, GsMTx-4 (2 μM), led to significant increases in CYM in male (R), female (R) and female (H) but not male (H). In contrast, in endothelial denuded vessels, GsMTx-4 produced a significant increase in CYM but only in females (R). These findings point to sex-specific changes in the ultrastructure and function of these arteries, which seem to alter the biomechanics and, thus, ultimately, the integrated function of macro- and micro-circulations.