No abstract

The idea that Na(+) retention inevitably leads to water retention is compelling; however, were Na(+) accumulation in part osmotically inactive, regulatory alternatives would be available. We speculated that in DOCA-salt rats Na(+) 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(+), K(+), and water were measured in skin, bone, muscle, and total body by desiccation and consecutive dry ashing. DOCA-salt led to total body Na(+) excess (0.255 +/- 0.022 vs. 0.170 +/- 0.010 mmol/g dry wt; P < 0.001), whereas water retention was only moderate (0.685 +/- 0.119 vs. 0.648 +/- 0.130 ml/g wet wt; P < 0.001). Muscle Na(+) retention (0.220 +/- 0.029 vs. 0.145 +/- 0.021 mmol/g dry wt; P < 0.01) in DOCA-salt was compensated by muscle K(+) loss, indicating osmotically neutral Na(+)/K(+) exchange. Skin Na(+) retention (0.267 +/- 0.049 vs. 0.152 +/- 0.014 mmol/g dry wt; P < 0.001) in DOCA-salt rats was not balanced by K(+) loss, indicating osmotically inactive skin Na(+) storage. We conclude that DOCA-salt leads to tissue Na(+) excess relative to water. The relative Na(+) excess is achieved by two distinct mechanisms, namely, osmotically inactive Na(+) storage and osmotically neutral Na(+) retention balanced by K(+) loss. This "internal Na(+) escape" allows the maintenance of volume homeostasis despite increased total body Na(+).

Abstract-Water-free Na ϩ storage may buffer extracellular volume and mean arterial pressure (MAP) in spite of Na ϩ retention. We studied the relationship among internal Na ϩ , K ϩ , water balance, and MAP in Sprague-Dawley rats, with or without deoxycorticosterone-acetate (DOCA) salt, with or without ovariectomy (OVX). The rats were fed a low-salt (0.1% NaCl) or high-salt (8% NaCl) diet for 5 weeks. DOCA salt increased MAP (161Ϯ14 versus 123Ϯ4 mm Hg; PϽ0.05), and DOCA-OVX salt increased MAP further (181Ϯ22 mm Hg; PϽ0.05). DOCA salt increased the total body Na ϩ by Ϸ40% to 45%; however, water-free Na ϩ retention by osmotically inactive Na ϩ storage and by osmotically neutral Na ϩ /K ϩ exchange allowed the rats to maintain the extracellular volume close to normal. DOCA-OVX salt rats showed similar Na ϩ retention. However, their osmotically inactive Na ϩ storage capacity was greatly reduced and only partially compensated by neutral Na ϩ /K ϩ exchange, resulting in greater volume retention despite similar Na ϩ retention. For every 1% wet weight total body water gain, MAP increased by 2.3Ϯ0.2 mm Hg in DOCA salt rats and 2.5Ϯ0.3 mm Hg in DOCA-OVX salt rats. Because water-free Na ϩ retention buffered total body water content by 8% to 11% wet weight, we conclude that this internal Na ϩ escape buffered MAP. Extrarenal Na ϩ and volume balance seem to play an important role in long-term volume and MAP control. Key Words: electrolytes Ⅲ gender Ⅲ water-electrolyte balance Ⅲ hypertension, sodium-dependent S alt sensitivity describes a reproducible relationship between increasing salt intake and blood pressure. 1 Blood pressure may increase because of increased cardiac output, increased peripheral resistance, or both. Volume-dependent and volume-independent factors contribute. Volumeindependent factors include autonomic nerve activity and molecules that modulate peripheral vascular resistance and heart muscle work. Volume-dependent aspects are based on extracellular fluid volume (ECV). Na ϩ is the major extracellular cation that osmotically acts to hold ECV water; the total body Na ϩ (TBNa ϩ ) has become synonymous for volume regulation. 2,3 Deoxycorticosterone-acetate (DOCA) decreases renal Na ϩ excretion and increases TBNa ϩ and total body volume. DOCA salt is a "prototype" model for salt-sensitive hypertension. 4 Secondary renin-angiotensin-aldosterone system suppression, 5 increased secretion of natriuretic peptides, 6 and altered pressure natriuresis 7 establish a new steady state between Na ϩ intake and Na ϩ excretion at a new blood pressure level. The kidneys escape the mineralocorticoid signal, and additional salt retention ceases, albeit with increased blood pressure. 8 We showed recently that DOCA rats given 1% saline accumulated 4.75 mmol Na ϩ . 9 Only 20% of this Na ϩ load exerted osmotic activity and led to water retention, whereas the rest accumulated as water free by osmotically inactive Na ϩ storage and/or osmotically neutral Na ϩ /K ϩ exchange. In Sprague-Dawley rats, we found that ovariectomy (OVX) reduced th...