Participation of Endogenous Atrial Natriuretic Peptide in the Regulation of Urinary Protein Excretion in Experimental Diabetic Rats

Author:

Hirata Yasunobu1,Suzuki Yasuko1,Hayakawa Hiroshi1,Suzuki Etsu1,Kimura Kenjiro1,Goto Atsuo1,Kangawa Kenji2,Matsuo Hisayuki2,Omata Masao1

Affiliation:

1. Second Department of Internal Medicine, University of Tokyo, Tokyo, Japan

2. National Cardiovascular Center Research Institute, Osaka, Japan

Abstract

1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats. 2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 ± 5 (SE) versus 115 ± 6 pg/ml, P < 0.01] and a higher glomerular filtration rate (3.3 ± 0.1 versus 2.7 ± 0.2 ml min−1 kg−1, P < 0.05). 3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats. 4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus. 5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (−61 ± 14%, P < 0.02) and protein (−51 ± 17%, P < 0.05). These changes were associated with a significant reduction in glomerular filtration rate (−32 ± 11%, P < 0.05) and urinary cGMP excretion (−40 ± 14%, P < 0.05). No significant effects of HS-42-1 on renal function were observed in control rats. 6. These results suggest that elevated plasma glucose may lead to an increase in atrial natriuretic peptide secretion via a rise in atrial pressure, which in turn results in increased urinary sodium and protein excretion. Elevated plasma atrial natriuretic peptide appears to contribute to the proteinuria in diabetic rats.

Publisher

Portland Press Ltd.

Subject

General Medicine

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