Hemodynamic role of extracellular fluid in hypertension

Abstract

Plasma volume is usually lower in patients with essential hypertension than in normal subjects. Normal or expanded plasma volume in some hypertensive patients may respect either a specific hypervolemic subset of the disease or the upper end of a continuum of volume values. Difficulties in defining these groups stem from the small numbers of subjects studied, from the need for a reliable reference index for volume measurements, and from the multiple factors which may affect intravascular volume. Differences in plasma volume cap influence choice of antihypertensive therapy; patients with expanded volume tend also to have slightly exchangeable sodium and greater extracellular fluid (ECF) volume and to respond well to diuretic therapy. There is also some evidence that low plasma renin activity is more frequent among hypervolemic patients. Essential hypertensives as a group have low plasma to interstitial fluid volume ratio (PV/IF), indicating that ECF distribution between the intravascular and interstitial compartments is shifted toward the latter. This is probably related to altered capillary filtration pressure due to increased venous resistance. Hypovolemic essential hypertensives have significantly lower (P less than 0.01) PV/IF ratio than hypervolemic, but whether this is related to differences in neural venous tone is only speculative. Hemodynamic studies revealed no difference in cardiac output between hypertensive patients with contracted blood volume and those with hypervolemia; total peripheral resistance was even higher in the latter, suggesting that "vasoconstriction" is not different between the two groups. It is widely believed that the relationship between ECF expansion and hypertension depends on the development of hypervolemia, increased cardiac output, and subsequent rise in total peripheral resistance reducing volume expansion and normalizing systemic flow while maintaining a high blood pressure. This sequence of events has been demonstrated in some human and experimental forms of hypertension but not in all. Metyrapone-induced hypertension in dogs could be sustained for up to 6 weeks by increased output with no evidence of "autoregulation" developing, and similar observations were reported in some anephric patients. Complementing these findings are observations of elevated cardiac output in some patients with long-standing essential hypertension or primary aldosteronism. It is therefore suggested that the spectrum of hemodynamic changes associated with volume disturbances in hypertension is too wide to be forced under one hypothesis alone and that neurogenic and other factors may play an important role in that complex relationship.