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) receptor function impairs Na excretion by the kidney. Thus we hypothesized that rats lacking functional ET receptors (ET-def) will have a reduced capacity of the skin to store Na during chronic high-salt (HS) intake. We observed that ET-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-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-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 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.

Knockout of the Circadian Clock Protein PER1 (Period1) Exacerbates Hypertension and Increases Kidney Injury in Dahl Salt-Sensitive Rats

“…The effect of diet to increase the mesor and the interaction of genotype and diet were also significant for the MAP mesor. Consistent with previous findings in rats, 19,20 the high-salt diet increased the amplitude of MAP, and this effect was independent of genotype.…”

Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats

“…There are no reported sex differences in osmotically inactive Na ϩ storage under normal salt conditions in rats (50), and under states of balanced intake and excretion, there is no significant Na ϩ mobilization between compartments. The imbalance in this buffering system has been reported only in states of excessive salt intake or under conditions of hypertension and chronic kidney disease (47).…”

Diurnal Regulation of Renal Electrolyte Excretion: The Role of Paracrine Factors

“…These results provide strong evidence for involvement of Bmal1 in ET-1 system-mediated regulation of renal sodium excretion. Of note, high salt diet causes an increase in skin sodium content during the active phase compared with inactive phase in ET B -def rats, which may contribute to the increased blood pressure amplitude observed in these rats following high salt diet (48).…”