Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species
(2016) In American Journal of Physiology: Renal, Fluid and Electrolyte Physiology 311(5). p.984-990- Abstract
There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with eitherL-NAME orL-NAME together with the superoxide... (More)
There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with eitherL-NAME orL-NAME together with the superoxide scavenger Tempol, or together withL-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h.L-NAME increased θ for Ficoll70Å from 2.27 ± 1.30 ˟ 10-5 to 8.46 ± 2.06 ˟ 10-5 (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed withL-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo byL-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.
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- author
- Dolinina, Julia LU ; ÖRN SVERRISSON, KRISTINN LU ; Rippe, Anna LU ; Öberg, Carl M. LU and Rippe, Bengt LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Capillary permeability, CGMP, Ficoll, Glomerular filtration, Glomerular sieving coefficient, Soluble guanylyl cyclase
- in
- American Journal of Physiology: Renal, Fluid and Electrolyte Physiology
- volume
- 311
- issue
- 5
- pages
- 984 - 990
- publisher
- American Physiological Society
- external identifiers
-
- scopus:84995468866
- pmid:27681559
- wos:000389646700018
- ISSN
- 0363-6127
- DOI
- 10.1152/ajprenal.00152.2016
- language
- English
- LU publication?
- yes
- id
- 358b7342-8d49-4c2f-b796-48323064a951
- date added to LUP
- 2016-12-02 14:23:38
- date last changed
- 2024-06-14 19:11:14
@article{358b7342-8d49-4c2f-b796-48323064a951,
abstract = {{<p>There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with either<sub>L</sub>-NAME or<sub>L</sub>-NAME together with the superoxide scavenger Tempol, or together with<sub>L</sub>-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h.<sub>L</sub>-NAME increased θ for Ficoll<sub>70Å</sub> from 2.27 ± 1.30 ˟ 10<sup>-5</sup> to 8.46 ± 2.06 ˟ 10<sup>-5</sup> (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed with<sub>L</sub>-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo by<sub>L</sub>-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.</p>}},
author = {{Dolinina, Julia and ÖRN SVERRISSON, KRISTINN and Rippe, Anna and Öberg, Carl M. and Rippe, Bengt}},
issn = {{0363-6127}},
keywords = {{Capillary permeability; CGMP; Ficoll; Glomerular filtration; Glomerular sieving coefficient; Soluble guanylyl cyclase}},
language = {{eng}},
number = {{5}},
pages = {{984--990}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Renal, Fluid and Electrolyte Physiology}},
title = {{Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species}},
url = {{http://dx.doi.org/10.1152/ajprenal.00152.2016}},
doi = {{10.1152/ajprenal.00152.2016}},
volume = {{311}},
year = {{2016}},
}