Renal Interaction of Atrial Natriuretic Peptide With Angiotensin Ii: Glomerular and Tubular Effects

Abstract

1. The possible interactions between the renal effects of atrial natriuretic peptide (ANP) and angiotensin II (AII) were studied in normal sodium-replete human subjects. Recent investigations have suggested that ANP inhibits the pressor and volume-retaining effects of activation of the renin-angiotensin system. Thus, ANP may attenuate the effects of AII on renal haemodynamics or tubular transport. 2. ANP (0.1 micrograms/kg per min, 60 min) was intravenously infused into eight normal human subjects with and without pretreatment with enalapril (20 mg, per oral), an inhibitor of the converting enzyme, and during infusion of AII (10 mg/kg per min). 3. ANP infusion alone caused increases in the urine volume (from 96 +/- 23 to 229 +/- 44 mL/h, P less than 0.05) and urinary sodium excretion (from 11.5 +/- 1.6 to 20.9 +/- 4.2 mEq/h, P less than 0.05). These changes were accompanied by an increase in the glomerular filtration rate (from 127 +/- 9 to 158 +/- 9 mL/min, P less than 0.05). ANP infusion after enalapril administration lowered the mean blood pressure (from 76 +/- 2 to 71 +/- 3 mmHg, P less than 0.05) to a level similar to that observed during ANP infusion alone (from 84 +/- 2 to 74 +/- 2 mmHg, P less than 0.01), but did not result in a significant diuresis (from 139 +/- 23 to 174 +/- 51 mL/h) or natriuresis (from 19.7 +/- 2.5 to 14.3 +/- 3.4 mEq/h, P less than 0.05). This combined treatment with a converting enzyme inhibitor and ANP reduced both the glomerular filtration rate (160 +/- 9 to 141 +/- 10 mL/min) and the renal plasma flow (from 775 +/- 49 to 570 +/- 45 mL/min, P less than 0.01). 4. The antinatriuretic effects of exogenous AII were reversed by superimposed ANP infusion (urinary sodium excretion: from 4.8 +/- 1.0 to 24.3 +/- 5.2 mEq/h, P less than 0.01). Under these conditions, the glomerular filtration rate increased (from 114 +/- 6 to 156 +/- 7 mL/min, P less than 0.05) to levels similar to those observed with ANP infusion alone. In addition the increased tubular sodium reabsorption induced by AII was inhibited by concomitant ANP infusion (fractional proximal tubular sodium reabsorption: from 90.7 +/- 3.5 to 80.3 +/- 16.6%, P less than 0.05, fractional post-proximal tubular sodium reabsorption: from 91.5 +/- 9.8 to 87.6 +/- 8.8%, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Proximal Nephron

“…These whole-kidney studies on the effects of ANF on APR and GTB are consistent with the shrinking split-droplet micropuncture study of Harris et al in rat proximal convoluted tubules (198) or in isolated perfused proximal straight tubules as reported by Garvin (151). The other indirect evidence supporting our observations includes that ANF-induced increases in fractional lithium and phosphate excretion were abolished by combined administration of an ACE inhibitor and ANG II (420; 421; 438). However, it should be pointed out that Liu and Cogan failed to demonstrate a proximal tubular effect of ANF when it was administered at a pharmacological dose (5 µg/kg as a bolus dose followed by a constant infusion rate of 0.5 µg/kg/min) (318).…”

Renal and hormonal actions of atrial natriuretic peptide during angiotensin II or noradrenaline infusion in man

“…Thus a type 2 error and an attenuated natriuretic effect of ANP during ANG II infusion cannot be totally excluded. In contrast to the present study, Rakugi et al [23] found that ANG II in a pressor dose potentiates the natriuretic action of ANP in normal man, but the blood pressure increment may per se have affected the natriuretic response to ANP [24]. In healthy man, ACE inhibition has been reported to attenuate ANP-induced natriuresis [25], but the accompanying blood pressure reduction may at least in part have caused the attenuation.…”

Atrial natriuretic peptide in normal and pre-eclamptic human pregnancy

“…71,86 The difference between animal and human pregnancy may involve methodological as well as pharmacological factors, e.g. Increases in GFR are seen with high dose infusions 83,88,89 whereas GFR is decreased or unchanged with low dose ANP infusion. In the animal studies where pharmacological doses of ANP were given, pANP was boosted at least 5±10 fold above basal levels.…”

“…90±92 In contrast, low dose infusion of ANP in pre-eclampsia signi®cantly increases GFR, with ERPF remaining unchanged (see Table 1), changes normally associated with pharmacological doses of ANP, 83,88,89 i.e. 90±92 In contrast, low dose infusion of ANP in pre-eclampsia signi®cantly increases GFR, with ERPF remaining unchanged (see Table 1), changes normally associated with pharmacological doses of ANP, 83,88,89 i.e.…”