O. Vinot et al., ENDOGENOUS ANP IN POSTISCHEMIC ACUTE RENAL-ALLOGRAFT FAILURE, American journal of physiology. Renal, fluid and electrolyte physiology, 38(1), 1995, pp. 125-133
Circulating atrial natriuretic peptide (ANP) levels and glomerular bin
ding sites for ANP were examined in 23 subjects undergoing renal trans
plantation. Subjects were divided into two groups, group 1 (n = 12) wi
th prompt and group 2 (n = 11) with delayed allograft function. Sixty
to 180 min after graft reperfusion, renovascular resistance was threef
old higher and glomerular filtration rate (GFR) depressed by 79% in gr
oup 2 vs. group 1. Corresponding median plasma ANP (114 vs. 140 pg/ml)
and guanosine 3',5'-cyclic monophosphate (cGMP) levels (22 vs. 28 pmo
l/ml) were similarly elevated in the two groups [P = not significant (
NS)]. Autoradiographic analysis of glomeruli in an allograft biopsy re
vealed the median density of total receptors (24 vs. 28 fmol/mm(3)), A
receptors (15 vs. 19 fmol/mm(3)), and C receptors (6 vs. 9 fmol/mm(3)
) for ANP to also be similar in group 2 vs. group 1, respectively (P =
NS). By postoperative day 3, allograft GFR averaged only 6 +/- 2 in g
roup 2 vs. 59 +/- 4 ml/min in group 1. Median plasma ANP levels double
d in each group to 262 and 251 pg/ml, respectively (P = NS). However,
median values for plasma levels (38 vs. 17 pmol/ml) and the fractional
clearance of cGMP (1.9 vs. 1.2) were significantly higher in group 2
than group 1. We conclude that, despite an adequate density of glomeru
lar ANP receptors and enhanced cGMP generation, neither renal vasocons
triction nor hypofiltration is alleviated by a progressive elevation o
f plasma ANP levels in renal transplant recipients with sustained post
ischemic injury. We infer that constricted afferent arterioles are unr
esponsive to the vasorelaxant action of endogenous ANP in this form of
postischemic, acute renal failure.