Ontogeny of the renal response to natriuretic peptide in sheep

Abstract

The ontogeny of the renal response to continuous systemic infusion of atrial natriuretic peptide (ANP) was studied in chronically instrumented fetal, newborn, and adult nonpregnant sheep. Plasma immunoreactive ANP (ANPir) concentrations during low (0.025 microgram.kg-1.min-1) and high rate (0.1 microgram.kg-1.min-1) ANP infusion were similar between each group of animals. Decrease in renal blood flow velocity (RBFV) and rise in renal vascular resistance (RVR) were observed in fetal and newborn lambs during ANP infusion. The percent changes in RBFV and RVR were of significantly (P less than 0.05) greater magnitude during high ANP infusion rate in fetuses (-28.5 +/- 8.5 and 93 +/- 6.4%) than in adult sheep (-6.6 +/- 3.2 and -4.4 +/- 4.9%). ANP produced no changes in urine flow (V) in fetuses but increased V significantly in newborn lambs and adult sheep. Glomerular filtration rate increased significantly during ANP infusion in adult sheep but not in fetal and newborn lambs. Percentage changes in urinary excretion rate of Na (UNaV) during high ANP infusion rate were significantly higher in adult sheep (3,520 +/- 2,414%) than in newborn (157 +/- 106%) and fetal lambs (198 +/- 84%). These results suggest that the cardiovascular, renal hemodynamic, and possibly renal function responses to continuous ANP infusion increase during maturation, the overall response being larger in adult animals.

Atrial Natriuretic Peptide and Renal Haemodynamics in Newborn Calves

“…The above-mentioned results may support the suggestion by Granger (1998) that the lack of changes in the glomerular filtration rate results from ANP "redirecting" blood into the medullary part of the kidneys. Conversely, Janssen et al (1994) in adult humans, Robillard et al (1988) in adult sheep, Seino et al (1988) in adult rabbits, andChevalier et al (1988) in adult rats, observed an increased glomerular filtration rate after administration of exogenous ANP. According to Dunn et al (1986) and Marin-Grez et al (1986), enhanced GFR may be a result of haemodynamics changes in the blood vessels of the glomeruli which lead to elevated glomerular filtration pressure.…”

“…So far, it has not been clearly established whether and how atrial natriuretic peptide affects renal plasma filtration (Abu-Amarah and Balment 1999;Bidiville et al 1988;Chevalier et al 1988;Garcia-Estan and Roman 1990;Janssen et al 1994;Robillard et al 1988;Seino et al 1988;Semmekrot et al 1990). In our experiment, a lack of relationship was demonstrated between changes in ANP concentration in blood and glomerular filtration rate (coefficient of correlation non-significant at p ≤ 0.05).…”

“…However, the literature provides discrepant information on the influence of ANP on renal haemodynamics (Abu-Amarah and Balment 1999; Eiskjaer et al 1996;Garcia-Estan and Roman 1990;Janssen et al 1994;Semmekrot et al 1990). It has also been published that an effect of exogenous ANP on renal blood (and plasma) flow and glomerular filtration rate may depend on the age of the examined individuals (Chevalier et al 1988;Robillard et al 1988;Semmekrot et al 1990). …”

Role of Endogenous Atrial Natriuretic Peptide in Chronic Anemia in the Ovine Fetus: Effects of a Non-Peptide Antagonist for Atrial Natriuretic Peptide Receptor

“…A brief increase in renal blood flow occurred in the nonanemic fetuses as well. Consistent with these findings, Robillard et al (8) observed a decrease in renal blood flow and increasin g renal vascular resistance in ovine fetuses receiving exogenous ANP . Furthermore, our findings are consistent with previous studies in adult models: ANP increased renal vascular resistanc e in the isolated perfused rat kidney (25), and in some reports, but not others (26), ANP administered in vivo decreased renal blood flow in the euvolemic adult rat.…”

“…Circulating ANP concentrations are elevated in human fetuses with chronic anemia due to isoimmuni zation (5), as well as in experimental models of fetal hydrops and polyhydramnios (6), and ANP has been implicated in the pathogenesis of these conditions because it promotes vascular permeation of fluid and protein in the ovine fetus (7). The obse rvation that exogenously administered ANP causes increased sodium excretion when administered to otherwise normal fetuses (8) suggests that this hormon e may also enhance the natriuresis in prolonged fetal anemia.…”