Site of the action of a synthetic atrial natriuretic peptide evaluated in humans

Abstract

The renal site of the natriuretic effect of human, atrial natriuretic peptide (hANP) was studied using clearance techniques in eight salt-loaded normal volunteers undergoing maximal water diuresis. Lithium was used as a marker of proximal sodium reabsorption. According to a two-way, single blind, crossover design, hANP (Met12-(3-28)-eicosahexapeptide, (2 micrograms/min) or its vehicle (Ve) were infused for two hours, followed by a two-hour recovery period. Blood pressure, heart rate and insulin clearance remained unchanged. During hANP infusion, the filtration fraction increased slightly from 19.6 to 24.3% (P less than 0.001), fractional water excretion rose transiently at the beginning of the infusion. Fractional excretion of sodium increased markedly from 2.2% to 7.4% (P less than 0.001) but remained unchanged with Ve. ANP increased fractional excretion of lithium slightly from 46 to 58% (P less than 0.01), while it remained stable at 47% during Ve. The distal tubular rejection fraction of sodium calculated from sodium and lithium clearances rose markedly from 4.7 to 13% (P less than 0.001) and returned to 6.2% at the end of the recovery period. Thus, under salt loading and water diuresis conditions, hANP infusion did not alter GFR, but reduced proximal reabsorption of sodium, and markedly enhanced the fraction of sodium escaping distal tubular reabsorption, suggesting that hANP-induced natriuresis is due, for an important part, to inhibition of sodium reabsorption in the distal nephron.

Enhanced natriuretic effect of atrial natriuretic factor during mineralocorticoid escape in humans.

“…Fractional diluting segment reabsorption decreased as well, which is the opposite of the change caused by mineralocorticoid expansion. Such effects of ANF on renal sodium handling have been found previously by others 24 and by ourselves. 21 -n The rise in GFR after ANF was not larger during escape.…”

Atrial natriuretic peptide and urinary prostaglandins in man.

“…An influence by angiotensin II appears unlikely since ANP administration would be expected to suppress rather to enhance renin release (Maack et al, 1985). Moreover, in our study, the subjects were salt-loaded and exhibited a low renin already to start with (Biollaz et al, 1987). Similarly, plasma arginine vasopressin levels were very low (Biollaz et al, 1987) which also renders the participation of this hormone in the stimulated PG biosynthesis unlikely.…”

“…Moreover, in our study, the subjects were salt-loaded and exhibited a low renin already to start with (Biollaz et al, 1987). Similarly, plasma arginine vasopressin levels were very low (Biollaz et al, 1987) which also renders the participation of this hormone in the stimulated PG biosynthesis unlikely. Another possible factor could be the UFR per se since, in spite of some contradictory results (Scherer & Weber, 1979;Kramer et al, 1981;Fejes-Toth et al, 1983), many authors have reported that the urinary excretion of PGE2 (Walker et al, 1981;Kaojarern et al, 1984;Haylor et al, 1986) and TxB2 (Zipser & Smorlesi, 1984) were positively related to UFR.…”

“…The protocol was approved by the ethics committee of the CHU Vaudois and informed consent was given by all the subjects. The study protocol has been described in detail elsewhere (Biollaz et al, 1987). In short, during the 5 days before the experiment, the subjects who were asked to abstain from sexual activity received a normal diet supplemented with 85 mmol/day of NaCl.…”

Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans.

“…3334 Although documentation of the latter is inconsistent in direct studies, 35 in clearance studies such as the present one ERPF often falls or tends to fall while GFR rises. 24 - 44 Whereas preglomerular vasodilation promotes natriuresis by increasing GFR and peritubular hydrostatic pressure and flow, the postglomerular vasoconstriction might oppose natriuresis by decreasing peritubular pressure and flow. Ca 2+ entry blockade could have specifically pro-moted the dilatory effect of ANF, which is in agreement with data that indicate a preferential afferent arteriolar action of Ca 2+ entry blockers.…”