Role of extracellular volume expansion in the development of DOC-salt hypertension in the rat.

Abstract

SUMMARY Changes in inulin space, plasma and blood volume, exchangeable and "noninulin" sodium were studied during the prehypertensive, early and late hypertensive stages of deoxycorticosterone (DOC)-saJt administration in the rat. The effect of an acute water load in previously nephrectomized animals was also studied. Hypertension developed after 1 to 2 weeks of the DOC-salt regimen and was always preceded by enlargement of the inulin space and increased plasma and blood volume. Expansion of extracellular fluids receded when blood pressure started to rise but reappeared after 4 to 6 weeks of treatment. Plasma sodium was high only in the hypertensive groups. An acute water load increased blood pressure of normal rats and decreased blood pressure of DOC-salt early hypertensive rats. These findings suggest that extracellular volume expansion inhibits a vasopressor mechanism that involves vasopressin and could be stimulated by hypernatremia. (Hypertension 4: 620-624, 1982) KEY WORDS • body fluids • deoxycorticosterone • hypertension H YPERTENSION produced by deoxycorticosterone (DOC) and salt is usually included in the "volume-dependent" variety because it is regularly associated with the expansion of the extracellular volume 1 -2 at least at some stage of the disease. However, we have recently found that an acute extracellular expansion lowers rather than raises the blood pressure of early, nonexpanded DOC-salt hypertensive rats.3 This latter effect was tentatively ascribed to the inhibition of some vasopressor volume-dependent mechanism possibly involving vasopressin.The aim of this paper was to try to reconcile these apparently contradictory findings and to gain further insight into the problem by following the time course of changes in exchangeable sodium (Na) and extracellular body fluids during the prehypertensive, early, and late stages of hypertension. In addition we have studied the effect of an acute water load, which is the most powerful physiological inhibitor of vasopressin release on blood pressure. 4 Methods General ProcedureWe studied 105 male Wistar rats weighing approximately 250 g. We gave 71 rats a drinking fluid of 1% (w/v) saline supplemented with 0.2% KG in water, and 25 mg of DOC enantate (Schering, Argentina) in castor oil intramuscularly twice a week during 1 to 6 weeks. As controls we used 34 male rats of similar breed, who drank tap water. All animals were given normal rat chow. Systolic blood pressure was measured in the unrestrained awake animals at 30°C by the plethysmographic tail method before starting treatment and then at weekly intervals until the time of sacrifice. Reproducibility between successive readings was better than 10 mm Hg. Therefore, rats were considered hypertensive when differences between readings performed at different days exceeded this upper limit. Two series of experiments were conducted: in the first one the time course of changes in blood pressure, exchangeable Na, and body fluids were followed at different stages of the disease. The second series was aime...

Hemodynamic characteristics of conscious deoxycorticosterone acetate hypertensive rats.

“…However, according to VILLAMIL et al (1982), extracellular volume, plasma volume, and blood volume were all greater only in rats in which arterial pressure did not elevate in the first 1-2 weeks of DOCA and salt administration or in those in which it elevated at last in the 4th-6th week. These variables were almost normal in rats in which arterial pressure had risen in the first 1-2 weeks.…”

How does salt retention raise blood pressure?

“…The hypertension that develops as a result of salt retention, as in mineralocorticoid hypertension, is always preceded by increased plasma volume (42,113). In the chronic state, the elevated BP promotes a pressure natriuresis so that normal ECF volume is restored at the expense of (chronically) elevated pressure (110).…”

“…Mineralocorticoid excess, which causes salt and water retention (42,113), induces hypertension in humans (59). DOCA-salt hypertension, in which uninephrectomized animals are administered DOCA and placed on a high-salt diet, is a common model of hypertension in mice, rats, and other animals.…”

Neurohumoral mechanisms in deoxycorticosterone acetate (DOCA)–salt hypertension in rats

“…They proposed that NaCl levels or plasma osmolality triggered sympathoexcitation, leading to hypertension. While it has been reported that DOCA–salt hypertension is characterized by a small but significant, sustained increase in plasma sodium (Möhring et al 1972; Villamil et al 1982), others reported a small but significant increase only when plasma sodium and chloride were combined (O'Donaughy & Brooks, 2006). Even small increases in plasma sodium can enhance sympathetic tone, supporting a role for increased SNA in DOCA–salt hypertension.…”