Abstract
Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.
This review has examined the pathophysiology of vasopressin in the edematous disorders of cardiac failure, cirrhosis, nephrotic syndrome and pregnancy and proposed a unifying hypothesis of body fluid volume regulation. A decrease in the EABV secondary to either a decreased cardiac output or a decrease in peripheral arterial resistance is proposed as the initiator of sodium and water retention. This decreased EABV leads to nonosmotic release of vasopressin and to activation of the sympathetic nervous and renin-angiotensinaldosterone systems. Nonosmotic release of vasopressin leads to water retention while increased secretion of aldosterone, and failure to escape from the hormones sodium-retaining effect, leads to sodium retention in edematous disorders.
Exceptions to the above statements may exist in nephrotic syndrome and pregnancy. In nephrotic syndrome, the kidney is diseased and intrarenal mechanisms may lead to expansion of the arterial vascular tree and suppression of the renin-angiotensin-aldosterone system. In pregnancy, the increased glomerular filtration rate and increased distal delivery of sodium and water “aldosterone escape” to occur.
