Involvement of Piezo 1 channels in vascular stiffness in isolated small resistance arteries of male and female Dahl salt-sensitive hypertensive rats

Background and Purpose: Piezo are mechanosensitive non-selective cation channels that are suggested to be involved in vascular development and function. The aim of our study was to determine any sex-specific contributions of the mechanosensitive Piezo 1 channels in vascular biomechanics. Experimental Approach: Composite Young modulus (CYM) was determined using pressure myograph experimental approach using third order mesenteric arteries (intact and denuded) from Dahl salt-sensitive male and female normotensive and hypertensive rats (n = 8). The effects of Piezo 1 agonist (Yoda; 10 µM), and antagonist (GsMTx-4; 2 µM) were studied. The distribution of Piezo 1 was identified in mesenteric arteries using immunohistochemistry. Key Results: In intact blood vessels, no differences in CYM between the experimental groups were noted, the removal of the endothelium unmasked significant increases in CYM in normotensive males and corresponding females compared to hypertensive males. In the intact tissue, GsMTx-4 led to significant increases in CYM in hypertensive females and normotensive males and females. In contrast, in the denuded vessels, GsMTx-4, produced a significant increase in CYM but only in the female normotensive group. Differential expression of Piezo 1 mechanosensitive ion channels in small mesenteric arteries were also found. Conclusion and Implications: The outcomes from our studies support a greater contributions of Piezo 1 channels to the biomechanics of male hypertensive compared to male normotensive and female hypertensive animals. The evidence also points to a possible differential vasoregulatory role for Piezo 1 channels in endothelial versus vascular smooth cells, with a greater contributions in males than females.