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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

Osmotically inactive skin [Na.sup.+] storage is characterized by [Na.sup.+] accumulation without water accumulation in the skin. Negatively charged glycosaminoglycans (GAGs) may be important in skin [Na.sup.+] storage. We investigated changes in skin GAG content and key enzymes of GAG chain polymerization during osmotically inactive skin [Na.sup.+] storage. Female Sprague-Dawley rats were fed a 0.1% or 8% NaCl diet for 8 wk. Skin GAG content was measured by Western blot analysis, mRNA content of key dermatan sulfate polymerization enzymes was measured by real-time PCR. The [Na.sup.+] concentration in skin was determined by dry ashing. Skin [Na.sup.+] concentration during osmotically inactive [Na.sup.+] storage was 180-190 mmol/l. Increasing skin [Na.sup.+] coincided with increasing GAG content in cartilage and skin. Dietary NaCl loading coincided with increased chondroitin synthase mRNA content in the skin, whereas xylosyl transferase, biglycan, and decorin content were unchanged. We conclude that osmotically inactive skin [Na.sup.+] storage is an active process characterized by an increased GAG content in the reservoir tissue. Inhibition or disinhibition of GAG chain polymerization may regulate osmotically inactive [Na.sup.+] storage. hypertension; extracellular matrix; chondroitin synthase; elongation enzymes

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

Osmotically inactive skin Na+ storage is characterized by Na+ accumulation without water accumulation in the skin. Negatively charged glycosaminoglycans (GAGs) may be important in skin Na+ storage. We investigated changes in skin GAG content and key enzymes of GAG chain polymerization during osmotically inactive skin Na+ storage. Female Sprague-Dawley rats were fed a 0.1% or 8% NaC1 diet for 8 wk. Skin GAG content was measured by Western blot analysis, mRNA content of key dermatan sulfate polymerization enzymes was measured by real-time PCR. The Na+ concentration in skin was determined by dry ashing. Skin Na+ concentration during osmotically inactive Na+ storage was 180-190 mmol/1. Increasing skin Na+ coincided with increasing GAG content in cartilage and skin. Dietary NaC1 loading coincided with increased chondroitin synthase mRNA content in the skin, whereas xylosyl transferase, biglycan, and decorin content were unchanged. We conclude that osmotically inactive skin Na+ storage is an active process characterized by an increased GAG content in the reservoir tissue. Inhibition or disinhibition of GAG chain polymerization may regulate osmotically inactive Na+ storage. [ABSTRACT FROM AUTHOR]

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, femalefertile, and female OVX Sprague-Dawley (SD) rats were fed a high (8%)- or 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 +] (rTBNa[sup +]) and skin Na[sup +] (rSKNa[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 rTBNa[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 rSKNa[sup +] (P < 0.01) in the rats. A high-salt diet led to Na[sup +] accumulation (ΔSKNa[sup +]) in the skin in all SD rats. Osmotically inactive skin Na[sup +] accumulation was ∼66% of ΔSKNa[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. [ABSTRACT FROM AUTHOR]