Individual hypertensive patients showed the different response of blood pressure to salt-loading (salt-sensitivity) (Am J Med 1980). There are growing bodies of evidences suggesting that renal sympathetic nervous system plays a key role in the development of salt-sensitive (SS) hypertension. High salt diet increases renal sympathetic activity (RSNA) in salt-sensitive hypertensive rats, whereas salt loading decreases RSNA in normotensive rats (Hypertension 1992). Moreover, salt-induced modulation of the aortic baroreflex was associated with that of the central property, since reflex inhibition of RSNA by stimulation of the aortic depressor nerve was augmented in normotensive rats but attenuated in SS hypertensive rats (Hypertension 1997), suggesting the involvement of central sympathoexcitation in the pathogenesis of salt-sensitive hypertension. Moreover, salt-induced overproduction of oxidative stress in the brain may contribute to central sympathoexcitation in SS hypertensive rats (Hypertension 2007), CKD rats (Hypertension 2012) and obesity-induced hypertensive rats (Circulation 2009). Interestingly, patients with salt-sensitive hypertension are associated with salt-induced hemodynamic changes that are similar to the pattern evoked during defense reaction; vasoconstriction appeared in the kidney and the splanchnic area but prominent vasodilation in the skeletal muscle (Hypertension 1990), suggesting that sympathetic over-activity on a selective basis might be involved in the impaired renal function for sodium excretion and the increase in blood pressure with sodium loads in SS patients. Most recently, we found clarified the involvement of aberrant renal β-adrenergic receptor-WNK4 pathway in the development of SS hypertension through the increased sodium reabsorption in the distal nephron (Nat Med 2011). Taken together, Central sympathoexcitation with salt loading causes sympathetic overactivity in the kidney on a selective basis, leading to the activation of β-adrenergic receptor-WNK4 pathway and salt-sensitive hypertension.