Renal and hormonal effects and tolerance of an ANP analogue in healthy man

Abstract

The effect of an analogue of atrial natriuretic peptide (P-ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by the lithium clearance technique, and plasma levels of sodium and water homeostatic hormones, has been studied in 40 healthy males. Placebo or P-ANP 0.3, 1.5, or 3.0 micrograms.kg-1 bwt were given as an intravenous bolus injection to different groups. P-ANP did not cause any immediate change in GFR or RPF, but significant dose-dependent increases in filtration fraction, urinary flow rate and urinary excretion rate of sodium were detected during the first 30 min after administration. Proximal absolute and fractional tubular reabsorption and distal absolute tubular reabsorption of sodium did not change after injection of P-ANP, while the distal fractional reabsorption of sodium was reduced in a dose dependent manner during the first 30 min. Plasma angiotensin II and aldosterone were significantly increased 30 and 150 min after dosage, whereas plasma atrial natriuretic peptide, plasma arginine vasopressin, and urinary excretion of prostaglandin E2 were unchanged. Cyclic guanosine monophosphate both in plasma and urine were increased in a dose-dependent manner. P-ANP cause a significant reduction in diastolic blood pressure and an increase in pulse rate. Two subjects had vasovagal syncope 30-60 min after injection of P-ANP. It is concluded that P-ANP has natriuretic, diuretic and hypotensive properties in healthy man.

Human pharmacokinetics of an analogue of atrial natriuretic factor

“…This can explain its unexpectedly short duration of action on blood pressure and kidney function as described in a previous report [4]. Thus, the increased natriuresis and diastolic blood pressure induced by ANP-270 lasted for less than 30 min and 45 min, respectively, values comparable to or even shorter than the effects obtained using c~hANF in other studies [5,and Eiskja~r and Pedersen,unpublished data].…”

“…Inclusion criteria and detailed demographic data have been reported elsewhere [4]. Informed consent was obtained from all subjects according to the regulations of the local Ethics Committee.…”

Hemodynamic, autonomic and neurohormonal behaviour of familial amyloidotic polyneuropathy and neurally mediated syncope patients during supine and orthostatic stress

“…Eiskjaer et al [20] described two subjects who had vasovagal syncope 30-60 min after injection of P-ANP and concluded that P-ANP has natriuretic, diuretic and hypotensive properties in healthy men. In the first minutes of tilting, we did not observe any change in ANP or BNP levels in any group of patients.…”

Atrial natriuretic peptide in normal and pre-eclamptic human pregnancy

“…the achievement of a steady state before measuring sodium excretion and renal haemodynamics, which might require more time in late pregnancy when plasma volume and MCR are elevated. 90±92 In human pregnancy ANP produces a signi®cant reduction in ERPF and an increase in ®ltration fraction, similar to the ®ndings in the non-pregnant state 71,87 (Table 1). On the other hand, when physiological doses of ANP were given there was no attenuation in the hypotensive effects in late pregnancy compared to post partum controls.…”

“…66 In contrast, human pregnancy does not show an attenuation of the natriuretic effect of infused ANP. 6 Infused ANP could induce natriureseis via increased GFR, 83,85 via a tubular effect 84,86 or both 87 and any of these effects could be related to infusion dose. the achievement of a steady state before measuring sodium excretion and renal haemodynamics, which might require more time in late pregnancy when plasma volume and MCR are elevated.…”