Atrial natriuretic factor: Its (patho)physiological significance in humans

Abstract

The first human studies using relatively high-doses of ANF revealed similar effects as observed in the preceding animal reports, including effects on systemic vasculature (blood pressure fall, decrease in intravascular volume), renal vasculature (rise in GFR, fall in renal blood flow), renal electrolyte excretion (rises in many electrolytes), and changes in release of a number of different hormones. Whether all these changes are the result of direct ANF effects or secondary to a (single) primary event of the hormone remains to be determined. Certainly, it has been proven that more physiological doses of ANF fail to induce short-term changes in many of these parameters leaving only a rise in hematocrit, natriuresis and an inhibition of the RAAS as important detectable ANF effects in humans. This leads us to hypothesize that ANF is a "natriuretic" hormone with physiological significance. The primary function in humans is to regulate sodium homeostasis in response to changes in intravascular volume (cardiac atrial stretch). Induction of excess renal sodium excretion and extracellular volume shift appear to be the effector mechanisms. The exact mechanism of the natriuresis in humans still needs to be resolved. It appears however, that possibly a small rise in GFR, a reduction in proximal and distal tubular sodium reabsorption, as well as an ensuing medullary washout, are of importance. The pathophysiological role of ANF in human disease is unclear. One may find elevated plasma irANF levels and/or decreased responses to exogenous ANF in some disease states. Whether these findings are secondary to the disease state rather than the cause of the disease remains to be resolved. Therapeutic applications for ANF, or drugs that intervene in its production or receptor-binding, seem to be multiple. Most important could be the antihypertensive effect, although areas such as congestive heart failure, renal failure, liver cirrhosis and the nephrotic syndrome cannot be excluded. Although the data that have been gathered to date allowed us to draw some careful conclusions as to the (patho)physiological role of ANF, the exact place of ANF in sodium homeostatic control must still be better defined. To achieve this, we will need more carefully designed low-dose ANF infusion, as well as ANF-breakdown inhibitor studies. Even more promising, however, is the potential area of studies open to us when ANF-receptor (ant)agonists become available for human use.

Hyperaldosteronism and Hypertension

“…Mean ANF concentrations are reported to be similar, higher, or even lower in patients with essential hypertension, compared with normotensive subjects. 9,38 In the current study, in both populations, mean plasma ANF concentrations and urine cGMP excretion were higher in hypertensive than in normotensive subjects. Other investigators have also reported elevated ANF concentrations in patients with low-renin essential hypertension, as well as in patients with primary aldosteronism, possibly as a marker of an expanded vascular volume.…”

“…On protocol day 2, plasma ANF and arginine vasopressin (AVP) were measured after an overnight fast; AVP was also measured after a fluid challenge, as previously described. 9 Black subjects were reimbursed $25 for the outpatient visit and $200 for their inpatient participation. The protocols were approved by the appropriate Human Research Review Committees at both participating institutions.…”

“…Blood pressure was also measured in response to a standardized math stress test. 9 Plasma electrolytes were also measured on day 1, and a 24-hour urine was collected for measurement of sodium, potassium, and cyclic guanine monophosphate (cGMP) excretion. On protocol day 2, plasma ANF and arginine vasopressin (AVP) were measured after an overnight fast; AVP was also measured after a fluid challenge, as previously described.…”

“…9 Cyclic GMP is a second messenger for both ANF and nitric oxide, and urine cGMP excretion reflects both ANF and nitric oxide activity. 37 Circulating levels of ANF are increased in experimental models of volumedependent hypertension.…”

“…Plasma atrial natriuretic factor (ANF) concentrations were measured as an indirect index of extracellular fluid volume. 9 …”