Faculty Collaboration Database

Nitric oxide production by glomerular podocytes. Nitric Oxide 2018 Jan 30;72:24-31

Date

11/13/2017

Pubmed ID

29128399

Pubmed Central ID

PMC5776695

DOI

10.1016/j.niox.2017.11.005

Scopus ID

2-s2.0-85034073816 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Nitric Oxide (NO), a potent vasodilator and vital signaling molecule, has been shown to contribute to the regulation of glomerular ultrafiltration. However, whether changes in NO occur in podocytes during the pathogenesis of salt-sensitive hypertension has not yet been thoroughly examined. We showed here that podocytes produce NO, and further hypothesized that hypertensive animals would exhibit reduced NO production in these cells in response to various paracrine factors, which might contribute to the damage of glomeruli filtration barrier and development of proteinuria. To test this, we isolated glomeruli from the kidneys of Dahl salt-sensitive (SS) rats fed a low salt (LS; 0.4% NaCl) or high salt (HS; 4% NaCl, 3 weeks) diets and loaded podocytes with either a combination of NO and Ca²⁺ fluorophores (DAF-FM and Fura Red, respectively) or DAF-FM alone. Changes in fluorescence were observed with confocal microscopy in response to adenosine triphosphate (ATP), angiotensin II (Ang II), and hydrogen peroxide (H₂O₂). Application of Ang II resulted in activation of both NO and intracellular calcium ([Ca²⁺]_i) transients. In contrast, ATP promoted [Ca²⁺]_i transients, but did not have any effects on NO production. SS rats fed a HS diet for 3 weeks demonstrated impaired NO production: the response to Ang II or H₂O₂ in podocytes of glomeruli isolated from SS rats fed a HS diet was significantly reduced compared to rats fed a LS diet. Therefore, glomerular podocytes from hypertensive rats showed a diminished NO release in response to Ang II or oxidative stress, suggesting that podocytic NO signaling is dysfunctional in this condition and likely contributes to the development of kidney injury.

Author List

Palygin O, Ilatovskaya DV, Levchenko V, Endres BT, Geurts AM, Staruschenko A

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Calcium Signaling
Glomerular Filtration Barrier
Hydrogen Peroxide
Hypertension
Kidney Glomerulus
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Donors
Nitroso Compounds
Podocytes
Rats, Inbred Dahl
Sodium Chloride, Dietary