SUMMARY The transport and distribution of sodium, potassium, and water were examined in tail arteries of rats treated with deoxycorticosterone acetate (DOCA)-saline for 10 days, a time that marks the earliest onset of a rise of blood pressure in the strain (Wistar) used. The arteries were incubated for more than 20 hours to ensure that any change observed was sufficiently built in so that it could not readily be washed out. Three distinct changes were observed. First, the steady state transmembrane sodium gradient (operationally [NaVfNa],) was increased. Second, the amount of sodium excluded from participation in the sodium gradient, and hence probably bound, was increased. Third, after prolonged potassium depletion, the ouabain-insensitive loss of cell water and sodium that follows the readmittance of potassium was increased. These results suggest that fundamental embedded changes in sodium transport occur well before the blood pressure rises in response to DOCA-saline. (Hypertension 8: 592-599, 1986) KEY WORDS • hypertension deoxycorticosterone acetate sodium cell water vascular smooth muscle S TRUCTURAL changes have long been known to play an important role in the development and perhaps the initiation of the hypertensive process. 1 In general, only the physical aspects of these changes as they determine the geometry and hence the reactivity of the vascular wall have been denned. It is clear, however, that structural changes include the chemical configuration of the cell membrane and the cytoplasm and that, as determinants of ion permeability and distribution, these warrant equal consideration. Such changes should be sufficiently embedded to be discernible in the blood vessel maintained in vitro under artificial conditions. The present study was undertaken to examine this possibility insofar as it affects the transport and distribution of Na in the tail artery taken from rats treated with deoxycorticosterone acetate (DOCA)-saline for 10 days and incubated in various modified physiological salt solutions for 18 to 24 hours before analysis. Received April 16, 1985; accepted January 5, 1986. Materials and Methods Adult male rats of an inbred Wistar strain (Charles River Canada, Montreal, Quebec), weighing 300 g or more were used throughout in batches of 18 or 36 rats for each experiment. These batches were unilaterally nephrectomized under pentobarbitone sodium anesthesia; 3 to 7 days later, half of each batch was set aside as controls and half were injected subcutaneously with 0.5 ml of saline containing 12.5 mg of DOC A as a microcrystalline suspension. A second and third injection of 6.25 mg each were given on Days 4 and 7. Vehicle alone was administered to controls on the same schedule to ensure equal handling. The DOCAtreated rats were given 1 % saline as drinking water so that the effective agonist was the DOCA-saline combination. At the 1% level, saline alone has no significant eifect on blood pressure or on conventional indices of Na transport.