Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats

Lakhwinder Singh; Atul Arya; Sumeet Gupta

doi:10.1515/jbcpp-2017-0146

Article

Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats

Lakhwinder Singh , Atul Arya and Sumeet Gupta

Published/Copyright: April 19, 2018

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 29 Issue 5

Abstract

Background

Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in reduced nitric oxide level and low expression of endothelial nitric oxide synthase by which nitric oxide level get reduced. In the present study, we examined the role of ANP in reduced nitric oxide level, which may be responsible in controlling diabetic nephropathy in rats.

Methods

Serum nitrite/nitrate ratio, blood urea nitrogen, protein in urine, urinary output, serum creatinine, serum cholesterol, kidney weight, kidney hypertrophy, renal cortical collagen content, thiobarbituric acid level, and antioxidant enzymatic activities were assessed.

Results

Treatment with lisinopril (1 mg/kg) significantly attenuated diabetes-induced elevated glucose level, cholesterol level, and protein in urine concentration. Whereas ANP at low dose (5 μg/kg) has no effect on elevated markers of diabetic nephropathy, treatment with intermediate (10 μg/kg) and high-dose ANP (20 μg/kg) significantly attenuated the diabetes-induced increased blood urea nitrogen, protein in urine, urinary output, creatinine, cholesterol, kidney weight, kidney hypertrophy, renal collagen content, and thiobarbituric acid level and reduced endogenous antioxidant enzymatic activities. High dose of ANP was more effective in attenuating the diabetes-induced nephropathy, renal oxidative stress, and antioxidant enzyme activity as compared with the treatment with low-dose ANP (5 μg/kg), intermediate-dose ANP (10 μg/kg), or lisinopril (1 mg/kg, employed as standard agent). Administration of erythro-9-(2-hydroxy-3-nonyl)adenine, a phosphodiesterase-2 inhibitor (3 mg/kg), in combination with high-dose ANP significantly attenuated high-dose ANP induced ameliorative effects in diabetic nephropathy.

Conclusions

Taken together, these results indicate that diabetes-induced oxidative stress and lipid alterations may be responsible for the induction of nephropathy in diabetic rats. ANP at intermediate and high doses have prevented the development of diabetes-induced nephropathy by reducing the cholesterol level, protein in urine concentration, and renal oxidative stress and by increasing the nitrite/nitrate ratio, certainly providing the direct nephroprotective action.

Keywords: nitric oxide; oxidative stress; phosphodiesterase

Acknowledgments

We would like to thank the I. K. Gujral Punjab Technical University Jalandhar (India) for the support and encouragement.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-10-28

Accepted: 2018-03-17

Published Online: 2018-04-19

Published in Print: 2018-09-25

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2017-0146

Keywords for this article

nitric oxide; oxidative stress; phosphodiesterase