Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model

Abstract

Recent evidence suggested that Na can be stored in an osmotically inactive form. We investigated whether osmotically inactive Na storage is reduced in a rat model of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as well as Sprague-Dawley (SD) rats were fed a high (8%)-or low (0.1%)-NaCl diet for 4 wk (n ϭ 10/group). Mean arterial pressure (MAP) was measured at the end of the experiment. Wet and dry weights, water content, total body Na (TBS), and bone Na content were measured by dessication and dry ashing. MAP was higher in both Dahl strains than in SD rats. In SS rats, 8% NaCl led to Na accumulation, water retention, and hypertension due to impaired renal Na excretion. There was no dietary-induced Na retention in SR and SD rats. TBS was variable; nevertheless, TBS was significantly correlated with body water and MAP in all strains. However, the extent of Na-associated volume and MAP increases was strain specific. Osmotically inactive Na in SD rats was threefold higher than in SS and SR rats. Both SS and SR Dahl rat strains displayed reduced osmotically inactive Na storage capacity compared with SD controls. A predisposition to fluid accumulation and high blood pressure results from this alteration. Additional factors, including impaired renal Na excretion, probably contribute to hypertension in SS rats. Our results draw attention to the role of osmotically inactive Na storage. salt sensitive; bone sodium; Dahl rats THE RELATIONSHIP BETWEEN SALT intake and blood pressure has been extensively studied in humans and provides evidence that subpopulations of humans are sensitive to alterations in salt intake. A well-established animal model for salt-sensitive (SS) hypertension is the Dahl rat. SS rats develop hypertension when fed a high-NaCl diet (6). Salt-resistant (SR) Dahl rats developed increased blood pressure after they received a transplanted kidney from an SS donor animal. Conversely, transplantation of SR donor kidneys into SS rats lowers blood pressure (5, 10). Despite the fact that the glomerular filtration rate is not different between both strains (2, 14), SS rats have an impaired ability to excrete Na (1, 2). However, this feature does not fully explain the development of SS hypertension (11). Thus the role of Na retention in the development of hypertension is unclear.Recent studies on long-term Na balance in humans showed that high dietary Na consumption with Na retention does not necessarily lead to expansion of the extracellular volume (8). This finding suggests that Na might be stored in an osmotically inactive form. We studied the relationship between osmotically inactive Na storage, total body Na (TBS), total body water (TBW), and hypertension in Dahl SS rats and control animals. Our initial primary hypothesis was that Dahl SS rats exhibit a reduced capacity for osmotically inactive Na storage that would predispose these animals to volume retention and thus lead to SS hypertension. The secondary hypothesis was that osmotically inactive Na storage is also deficient in...

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