Functional implications of decreased renal cortical atrial natriuretic peptide binding in experimental diabetes

A. Benigni, N. Perico, J. Dadan, M. Gabanelli, M. Galbusera, P. Boccardo, T. Mennini, G. Remuzzi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glomerular hyperfiltration in streptozotocin-induced diabetes mellitus in rats may be mediated by atrial natriuretic peptide (ANP). We wanted to evaluate plasma levels of ANP and plasma volume in relation to renal ANP receptor density and affinity in rats 6 weeks after induction of diabetes. Plasma levels of immunoreactive ANP were significantly higher in hyperglycemic diabetic (75.2 ± 8.3 pg/ml) than in control animals (34.7 ± 8.1 pg/ml; p <0.01). Administration of insulin to keep diabetic rats normoglycemic normalized plasma levels of immunoreactive ANP (30.5 ± 5.2 pg/ml). In contrast, plasma volume did not show significant differences among the groups (hyperglycemic diabetes, 46.6 ± 3.8; normoglycemic diabetes, 42.4 ± 3.2; controls, 43.2 ± 2.0 ml/kg body wt). No correlation was found between plasma levels of immunoreactive ANP and plasma volume. By autoradiography a significant reduction in the number of renal cortical ANP receptors was observed in hyperglycemic diabetic rats as compared with controls. At variance, ANP receptor affinity did not change either in the cortex or in the medulla in hyperglycemic diabetics in comparison with control animals. The pathophysiological implication of cortical ANP receptor down-regulation was underscored by the blunted response of glomerular filtration rate to ANP infusion in diabetic animals as compared with controls. These results indicate that in hyperglycemic diabetic rats: 1) the plasma volume is numerically higher without reaching a statistically significant value and does not correlate with the elevated plasma levels of ANP; 2) the marked rise in plasma concentration of ANP is associated with a significant reduction in the density of ANP binding sites in the renal cortex, without measurable changes in medullary receptors; and 3) the blunted glomerular hemodynamic response to ANP infusion underscores the importance of down-regulation of cortical ANP receptors in modulating the sustained hyperfiltration of early diabetes.

Original languageEnglish
Pages (from-to)1453-1460
Number of pages8
JournalCirculation Research
Volume66
Issue number6
Publication statusPublished - 1990

Fingerprint

Atrial Natriuretic Factor
Atrial Natriuretic Factor Receptors
Kidney
Plasma Volume
Down-Regulation
Experimental Diabetes Mellitus
Autoradiography
Glomerular Filtration Rate
Diabetes Mellitus
Hemodynamics
Binding Sites
Insulin

Keywords

  • atrial natriuretic peptide
  • autoradiography
  • diabetes
  • down-regulation
  • receptor
  • renal ANP receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Functional implications of decreased renal cortical atrial natriuretic peptide binding in experimental diabetes. / Benigni, A.; Perico, N.; Dadan, J.; Gabanelli, M.; Galbusera, M.; Boccardo, P.; Mennini, T.; Remuzzi, G.

In: Circulation Research, Vol. 66, No. 6, 1990, p. 1453-1460.

Research output: Contribution to journalArticle

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abstract = "Glomerular hyperfiltration in streptozotocin-induced diabetes mellitus in rats may be mediated by atrial natriuretic peptide (ANP). We wanted to evaluate plasma levels of ANP and plasma volume in relation to renal ANP receptor density and affinity in rats 6 weeks after induction of diabetes. Plasma levels of immunoreactive ANP were significantly higher in hyperglycemic diabetic (75.2 ± 8.3 pg/ml) than in control animals (34.7 ± 8.1 pg/ml; p <0.01). Administration of insulin to keep diabetic rats normoglycemic normalized plasma levels of immunoreactive ANP (30.5 ± 5.2 pg/ml). In contrast, plasma volume did not show significant differences among the groups (hyperglycemic diabetes, 46.6 ± 3.8; normoglycemic diabetes, 42.4 ± 3.2; controls, 43.2 ± 2.0 ml/kg body wt). No correlation was found between plasma levels of immunoreactive ANP and plasma volume. By autoradiography a significant reduction in the number of renal cortical ANP receptors was observed in hyperglycemic diabetic rats as compared with controls. At variance, ANP receptor affinity did not change either in the cortex or in the medulla in hyperglycemic diabetics in comparison with control animals. The pathophysiological implication of cortical ANP receptor down-regulation was underscored by the blunted response of glomerular filtration rate to ANP infusion in diabetic animals as compared with controls. These results indicate that in hyperglycemic diabetic rats: 1) the plasma volume is numerically higher without reaching a statistically significant value and does not correlate with the elevated plasma levels of ANP; 2) the marked rise in plasma concentration of ANP is associated with a significant reduction in the density of ANP binding sites in the renal cortex, without measurable changes in medullary receptors; and 3) the blunted glomerular hemodynamic response to ANP infusion underscores the importance of down-regulation of cortical ANP receptors in modulating the sustained hyperfiltration of early diabetes.",
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AU - Boccardo, P.

AU - Mennini, T.

AU - Remuzzi, G.

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AB - Glomerular hyperfiltration in streptozotocin-induced diabetes mellitus in rats may be mediated by atrial natriuretic peptide (ANP). We wanted to evaluate plasma levels of ANP and plasma volume in relation to renal ANP receptor density and affinity in rats 6 weeks after induction of diabetes. Plasma levels of immunoreactive ANP were significantly higher in hyperglycemic diabetic (75.2 ± 8.3 pg/ml) than in control animals (34.7 ± 8.1 pg/ml; p <0.01). Administration of insulin to keep diabetic rats normoglycemic normalized plasma levels of immunoreactive ANP (30.5 ± 5.2 pg/ml). In contrast, plasma volume did not show significant differences among the groups (hyperglycemic diabetes, 46.6 ± 3.8; normoglycemic diabetes, 42.4 ± 3.2; controls, 43.2 ± 2.0 ml/kg body wt). No correlation was found between plasma levels of immunoreactive ANP and plasma volume. By autoradiography a significant reduction in the number of renal cortical ANP receptors was observed in hyperglycemic diabetic rats as compared with controls. At variance, ANP receptor affinity did not change either in the cortex or in the medulla in hyperglycemic diabetics in comparison with control animals. The pathophysiological implication of cortical ANP receptor down-regulation was underscored by the blunted response of glomerular filtration rate to ANP infusion in diabetic animals as compared with controls. These results indicate that in hyperglycemic diabetic rats: 1) the plasma volume is numerically higher without reaching a statistically significant value and does not correlate with the elevated plasma levels of ANP; 2) the marked rise in plasma concentration of ANP is associated with a significant reduction in the density of ANP binding sites in the renal cortex, without measurable changes in medullary receptors; and 3) the blunted glomerular hemodynamic response to ANP infusion underscores the importance of down-regulation of cortical ANP receptors in modulating the sustained hyperfiltration of early diabetes.

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