Distribution of extracellular fluid over the intra- and extravascular space in hypertensive patients

The time course of hemodynamic responses to long-standing sodium overload was studied in humans. The study involved six patients who became hypertensive on exposure to excessive mineralocorticoid activity. Arterial pressure, cardiac output, and body fluid volumes were measured with noninvasive methods at weekly intervals for at least 6 weeks and at longer intervals for periods up to 2 years. Extracellular fluid volume was expanded by approximately 20%, and arterial blood pressure rose by 20-40%. Initially, cardiac output was the dominant factor for the pressure rise. But in a later stage the pressure remained high or rose even further, although cardiac output and body fluid volumes fell toward normal. In some cases, particularly in young subjects, it took weeks or months before the total peripheral resistance began to rise, and there was no quantitative relationship between the initial rise in cardiac output and the subsequent rise in resistance. These findings argue against a direct cause-and-effect relation between flow and resistance changes. Preferential expansion of the intravascular compartment was associated with high cardiac output, whereas preferential expansion of the interstitial fluid compartment was associated with high resistance. Thus, the hemodynamic pattern of sodium-induced hypertension seems somehow related to the distribution of extracellular fluid over the intra- and extravascular compartments.