Renal mechanism of action of rat atrial natriuretic factor.

Abstract

There has been conflict as to whether crude extracts of atrial natriuretic factor increase renal solute excretion by a hemodynamic mechanism or by direct inhibition of tubular transport. To investigate this issue, seven rats were studied during a euvolemic control period and following continuous administration of pure, synthetic 24 amino acid atrial natriuretic factor. A 10-25-fold increase in urinary sodium and chloride excretion occurred with a brisk kaliuresis but little bicarbonaturia. Atrial natriuretic factor caused whole kidney glomerular filtration rate to increase from 1.17±0.04 to 1.52±0.07 ml/min (P < 0.005). A parallel increase in single nephron glomerular filtration rate, from 34±1 to 44±2 nl/min (P < 0.001), and from 26±1 to 37±2 nl/min (P < 0.005) was measured at the end-proximal and early distal nephron sites, respectively. Appropriate for the higher flows were an increase in absolute proximal and loop reabsorptive rates for bicarbonate, chloride, and water, with a slight decrease in fractional solute and volume reabsorption in proximal and loop segments. To exclude the possibility that atrial natriuretic factor increased filtration rate only in anesthetized animals, eight unanesthetized rats were studied. Glomerular filtration rate increased by 45%, from 2.04±0.17 to 2.97±0.27 ml/min (P < 0.005) without significant change in renal plasma flow, as reflected by 14C-para-aminohippurate clearance (5.4±0.5-5.6±0.9 ml/min). The clearance and micropuncture data did not preclude changes in relative blood flow distribution to or in transport by deep nephron segments. In conclusion, atrial natriuretic factor appears to increase renal solute excretion predominantly by a hemodynamic mechanism without directly inhibiting superficial tubular transport.

The effects of atrial natriuretic peptide on renal function and the renin-aldosterone system in anesthetized rabbits.

“…In previous reports in which atrial natriuretic peptides or atrial natriuretic factors were infused into the renal artery or intravenously to anesthetized animals, a significant increase in GFR was observed during infusion of the peptides Beasley and Malvin 1985;Huang et al 1985). It is not clear why intravenous infusion of ANP failed to increase GFR significantly in the present experiment, but ANP used in the present study was a small dose.…”

“…But the mechanism by which atrial extract or atrial natriuretic peptide produces a natriuresis and diuresis is still unclear. Some studies have suggested that contribution of an increase in renal blood flow (Keeler and Azzarolo 1983;Wakitani et al 1985) or glomerular filtration rate Maack et al 1984 ; Beasley and Malvin 1985;Huang et al 1985) to the natriuresis and diuresis, and others have indicated direct tubular effects (Briggs et al 1982; Sonnenberg et al 1982; Pollock and Banks 1983; Burnett et al 1984Burnett et al , 1986Hammond et al 1985).…”

Enalapril attenuates natriuresis of atrial natriuretic factor in humans.

“…Yet, due to the marked rise in GFR, absolute sodium reabsorption may have been increased, in conformity with animal studies. 27 The main feature of this study is that the natriuretic effect of ANF was attenuated during enalapril treatment. In addition, the rise in GFR, solute free water clearance, phosphate, uric acid, and magnesium excretion and the fall in lithium reabsorption were blunted and nonsignificant.…”

“…27 ' 32 This would leave unexplained the increased excretion after administration of ANF of lithium, phosphate, and uric acid, alleged indicators of proximal tubular sodium reabsorption. 16 …”

Atrial natriuretic factor in mild to moderate chronic renal failure.

“…However, the filtration fraction rose progressively by up to 30%, as noted^jreviously in normal subjects, 4 hypertensive patients, 27 and experimental animals. 37 When possible humoral mediators were considered, plasma renin and aldosterone levels were largely unchanged during human ANF-(99-126) infusion, but they rose (p < 0.05-0.01) during the recovery phase in the renal patients. The latter reaction probably reflects overshoot following a human ANF-(99-126)-induced inhibition of renin secretion and adrenocortical function.…”