Diurnal pattern in skin Na⁺ and water content is associated with salt-sensitive hypertension in ET_B receptor-deficient rats

Abstract

Impairment in the ability of the skin to properly store Na⁺ nonosmotically (without water) has recently been hypothesized as contributing to salt-sensitive hypertension. Our laboratory has shown that endothelial production of endothelin-1 (ET-1) is crucial to skin Na⁺ handling. Furthermore, it is well established that loss of endothelin type B receptor (ET_B) receptor function impairs Na⁺ excretion by the kidney. Thus we hypothesized that rats lacking functional ET_B receptors (ET_B-def) will have a reduced capacity of the skin to store Na⁺ during chronic high-salt (HS) intake. We observed that ET_B-def rats exhibited salt-sensitive hypertension with an approximate doubling in the diurnal amplitude of mean arterial pressure compared with genetic control rats on a HS diet. Two weeks of HS diet significantly increased skin Na⁺ content relative to water; however, there was no significant difference between control and ET_B-def rats. Interestingly, HS intake led to a 19% increase in skin Na⁺ and 16% increase in water content (relative to dry wt.) during the active phase (zeitgeber time 16) versus inactive phase (zeitgeber time 4, P < 0.05) in ET_B-def rats. There was no significant circadian variation in total skin Na⁺ or water content of control rats fed normal or HS. These data indicate that ET_B receptors have little influence on the ability to store Na⁺ nonosmotically in the skin during long-term HS intake but, rather, appear to regulate diurnal rhythms in skin Na⁺ content and circadian blood pressure rhythms associated with a HS diet.