Article
DOCA-salt is a largely volume-independent hypertension and is influenced by ovarian function
Entwicklung von Hypertonie bei DOCA-salzbehandelten Ratten ist weitgehend unabhängig vom Flüssigkeitsvolumen im Körper und verschlechtert sich nach Ovariektomie
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Published: | August 8, 2006 |
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Background: Recent evidence suggests that water-free Na+ storage is a regulatory alternative to maintain the extracellular volume (ECV) in spite of Na+ retention. We speculated that osmotically inactive Na+ storage maintains the ECV and hence mean arterial blood pressure (MAP) in DOCA-salt rats.
Methods: Fifty-two female Sprague Dawley rats were assigned to 6 groups. Groups 1 and 2 were untreated, groups 3 and 4 received DOCA treatment. Groups 5 and 6 were ovariectomized (OVX) and DOCA treated. Groups 1, 3, and 5 were fed a <0.1% NaCl, the other groups received an 8% NaCl chow. MAP was measured at the end of the experiment. After sacrifice, all rats were dry ashed and internal Na+, K+, and water balance was determined. Osmotically inactive Na+ storage was assessed from the relationship between Na+, K+, and water in the tissue.
Results: DOCA-salt increased MAP (161±14 versus 123±4; p<0.05), and DOCA-OVX-salt increased MAP further (181±22 mmHg; p<0.05). DOCA-salt rats accumulated 4 mmol of Na+, of which only 0.82 mmol were accumulated as osmotically active, increaseing the ECV. Na+ mainly was accumulated water-free, either by osmotically neutral Na+/K+ exchange (1.41 mmol), or by osmotically inactive Na+ storage (1.77 mmol). DOCA-OVX-salt rats had a reduced osmotically inactive Na+ storage capacity. They accumulated 4.1 mmol of Na+, of which 2.14 mmol were retained water-free by Na+/K+ exchange. Only 0.43 mmol were retained as osmotically inactive, resulting in augmented volume retention in OVX rats despite similar Na+ retention. A 1% total body water (rTBW) increase resulted in a 2.3±0.2 mmHg MAP increase in DOCA-salt rats, and in a 2.5±0.3 mmHg MAP increase in DOCA-OVX-salt rats. As rTBW was increased by 2.7% in DOCA-salt rats, and by 4.4% in DOCA-OVX-salt rats, at most 15%-20% of the observed MAP increase rats had been volume-sensitive in both DOCA models.
Conclusions: DOCA-salt treatment increased the total body Na+ to ≈ 40-45%, however, water-free Na+ retention allowed the organism to maintain the ECV and hence may have a net depressive effect on MAP. Additional OVX resulted in a reduced water-free Na+ storage capacity with ECV and MAP increase. Besides these volume-sensitive aspects, hypertension with DOCA-salt was mainly volume-independent.