THE ROLE OF CHANGES OF BODY FLUID DISTRIBUTION IN ONSET AND MAINTENANCE OF DOCA-SALT HYPERTENSION RATS
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Body fluid distribution in DOCA-salt hypertension rats was measured by means of isotope dilution method in prehypertensive, early and chronic stages of hypertension. Plasma volume (PV), extracellular fluid volume (EFV) and total body water (TBW) were determined using 131-I-RISA, 35-S-Na<SUB>2</SUB>SO<SUB>4</SUB> and tritiated water, respectively. Mean arterial pressure (MAP) was measured directly through a carotid artery. Plasma renin activity (PRA) was also determined.<BR>Three experiments were performed under unanesthetized rats. Experiment 1 : Body fluid volumes in DOCA-salt treated rats on 3 day after DOCA-salt treatment were normotensive in spite of increased PV. The DOCA-salt rats on 7 day were still normotensive, whereas EFV and calculated interstitial fluid volume (IFV) were prominently increased without an increase in PV. The DOCA-salt rats on 14 day revealed elevated arterial pressure, but there were no significant differences in any of body fluid compartments as compared to control groups which were given only salt. The values of PRA in the DOCA-salt groups both on 3 day and 7 day were prominently suppressed and PRA in DOCA-salt group on 14 day was lower than those in the control group.<BR>Experiment 2 : DOCA-treated rats were divided into three groups which were given three graded salt intake ; high, normal, and low salt intakes. Control groups of rats were given the same three graded salt intakes as in the DOCA-treated rats. MAP and body fluid volume determination were performed on 28 day. The groups of DOCA with high salt and with normal salt were hypertensive, and no statistical difference was observed in MAP between them. Only the DOCA with high salt group had increased body fluid volumes, which were distributed proportionally among the PV, EFV, and calculated intracellular fluid volume (ICFV). The DOCA with normal salt and low salt group had no excess in body fluid volumes. The values of PRA in both DOCA with high and normal salt group were extremely suppressed, while those in DOCA with low salt group were not. Experiment 3 : Another group of DOCA with high salt was made, in which sodium was restricted for 2 weeks from 29 day after DOCA and salt treatment. The MAP in this group fell to control levels without significant changes in PV, while IFV was reduced to nomal levels.<BR>These results indicate that 1) in DOCA-salt treated rats, MAP elevation was preceded by increase in PV, following the normalization of PV in place of increase in IFV. There was no measurable increment of body fluid volumes in DOCA-salt treated rats at the early stage of hypertension ; however, the fluid volume changes in extracellular fluid compartments may be related to the initial pressure rise in DOCA-salt hypertension. 2) The excess in body fluid volume in chronic stage of DOCA induced hypertension is not necessary for DOCA to maintain hypertension, because there was expansion of body fluid volumes in DOCA with high salt group while no increase in body fluid volume in DOCA with normal salt group, and there was no significant difference in elevated MAP between them. 3) PRA suppression under DOCA administration as observed in experiment 1 and 2, is not induced simply by the expansion of body fluid volumes.
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