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

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.