Using the inbred Spontaneously Hypertensive Rat–Stroke Prone strain (SHRSP), a well-established rat model with many features of sporadic human SVD [57–59], we previously demonstrated intrinsically dysfunctional ECs with reduced endothelial nitric oxide synthase (eNOS) and secondary white matter changes in young rats prior to onset of hypertension, due to block of oligodendroglial maturation through increased EC secretion of Heat Shock Protein 90 alpha (HSP90α) [44]. Here, NOS3 is linked to Hypertension.