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The idea that [Na.sup.+] retention inevitably leads to water retention is compelling; however, were [Na.sup.+] accumulation in part osmotically inactive, regulatory alternatives would be available. We speculated that in DOCA-salt rats [Na.sup.+] accumulation is excessive relative to water. Forty female Sprague-Dawley rats were divided into four subgroups. Groups 1 and 2 (controls) received tap water or 1% saline (salt) for 5 wk. Groups 3 and 4 received subcutaneous DOCA pellets and tap water or salt. [Na.sup.+], [K.sup.+], and water were measured in skin, bone, muscle, and total body by desiccation and consecutive dry ashing. DOCA-salt led to total body [Na.sup.+] excess (0.255 [+ or -] 0.022 vs. 0.170 [+ or -] 0.010 mmol/g dry wt; P < 0.001), whereas water retention was only moderate (0.685 [+ or -] 0.119 vs. 0.648 [+ or -] 0.130 ml/g wet wt; P < 0.001). Muscle [Na.sup.+] retention (0.220 [+ or -] 0.029 vs. 0.145 [+ or -] 0.021 mmol/g dry wt; P < 0.01) in DOCA-salt was compensated by muscle [K.sup.+] loss, indicating osmotically neutral [Na.sup.+]/[K.sup.+] exchange. Skin [Na.sup.+] retention (0.267 [+ or -] 0.049 vs. 0.152 [+ or -] 0.014 mmol/g dry wt; P < 0.001) in DOCA-salt rats was not balanced by [K.sup.+] loss, indicating osmotically inactive skin [Na.sup.+] storage. We conclude that DOCA-salt leads to tissue [Na.sup.+] excess relative to water. The relative [Na.sup.+] excess is achieved by two distinct mechanisms, namely, osmotically inactive [Na.sup.+] storage and osmotically neutral [Na.sup.+] retention balanced by [K.sup.+] loss. This 'internal [Na.sup.+] escape' allows the maintenance of volume homeostasis despite increased total body [Na.sup.+]. hypertension; sodium storage; hypertensive rats; mineralocorticoid escape

Compared with age-matched men, women are resistant to the hypertensive effects of dietary NaCl; however, after menopause, the incidence of salt-sensitive hypertension is similar in women and men. We recently suggested that osmotically inactive [Na.sup.+] storage contributes to the development of salt-sensitive hypertension. The connective tissues, including those immediately below the skin that may serve as a reservoir for osmotically inactive [Na.sup.+] storage, are affected by menopause. We tested the hypothesis that ovariectomy (OVX) might reduce osmotically inactive [Na.sup.+] storage capacity in the body, particularly in the skin. Male, female-fertile, and female OVX Sprague-Dawley (SD) rats were fed a high (8%)- of low (0.1%)-NaCl diet. The groups received the diet for 4 or 8 wk. At the end of the experiment, subgroups received 0.9% saline infusion and urinary [Na.sup.+] and [K.sup.+] excretion was measured. Wet and dry weight (DW), water content in the body and skin, total body [Na.sup.+] (rTB[Na.sup.+]) and skin [Na.sup.+] (rSK[Na.sup.+]) content were measured relative to DW by desiccation and dry ashing. There were no gender differences in osmotically inactive [Na.sup.+] storage in SD rats. All SD rats accumulated [Na.sup.+] if fed 8% NaCl, but rTB[Na.sup.+] was lower in OVX rats than in fertile rats on a low (P < 0.001)- and a high (P < 0.05)-salt diet. OVX decreased rSK[Na.sup.+] (P < 0.01) in the rats. A high-salt diet led to [Na.sup.+] accumulation ([DELTA]SK[Na.sup.+]) in the skin in all SD rats. Osmotically inactive skin [Na.sup.+] accumulation was ~66% of [DELTA]SK[Na.sup.+] in female and 82% in male-fertile rats, but there was no osmotically inactive [Na.sup.+] accumulation in OVX rats fed 8% NaCl. We conclude that skin is an osmotically inactive [Na.sup.+] reservoir that accumulates [Na.sup.+] when dietary NaCl is excessive. OVX leads to an acquired reduction of osmotically inactive [Na.sup.+] storage in SD rats that predisposes the rats to volume excess despite a reduced [Na.sup.+] content relative to body weight. ovariectomy; sodium reservoir; total body sodium; Dahl rats; hypertension

Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model. Am J Physiol Renal Physiol 283: F134-F141, 2002. First published January 29, 2002; 10.1152/ajprenal.00323.2001.--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 = 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