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DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats

DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats
DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats
Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) share signaling and vasorelaxant properties and are involved in proliferation and apoptosis. Inhibiting NO production or availability induces hypertension and proteinuria, which is prevented by concomitant blockade of the H2S producing enzyme cystathionine ?-lyase (CSE) by D,L-propargylglycine (PAG). We hypothesized that blocking H2S production ameliorates Angiotensin II (AngII)-induced hypertension and renal injury in a rodent model. Effects of concomitant administration of PAG or saline were therefore studied in healthy (CON) and AngII hypertensive rats. In CON rats, PAG did not affect systolic blood pressure (SBP), but slightly increased proteinuria. In AngII rats PAG reduced SBP, proteinuria and plasma creatinine (180±12 vs. 211±19 mmHg; 66±35 vs. 346±92 mg/24h; 24±6 vs. 47±15 ?mol/L, respectively; p<0.01). Unexpectedly, kidney to body weight ratio was increased in all groups by PAG (p<0.05). Renal injury induced by AngII was reduced by PAG (p<0.001). HO-1 gene expression was increased by PAG alone (p<0.05). PAG increased inner cortical tubular cell proliferation after 1 week and decreased outer cortical tubular nucleus number/field after 4 weeks. In vitro proximal tubular cell size increased after exposure to PAG. In summary, blocking H2S production with PAG reduced SBP and renal injury in AngII infused rats. Independent of the cardiovascular and renal effects, PAG increased HO-1 gene expression and kidney weight. PAG alone increased tubular cell size and proliferation in-vivo and in-vitro. Our results are indicative of a complex interplay of gasotransmitter signaling/action of mutually compensatory nature in the kidney.
hydrogen sulfide, dl-propargylglycine, angiotensin-II, proteinuria, hypertension, kidney weight
1089-8603
56-66
Oosterhuis, Nynke R.
5de6affa-4f63-4694-8984-9ab10a65178d
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
Wesseling, Sebastiaan
add12e02-11da-4a03-835f-718ecaecc7ad
Snijder, Pauline M.
2599539b-34f7-4db3-aa91-0798f99c48a5
Slaats, Gisela G.
23d0d509-bc29-403d-a658-75f42002be7a
Yazdani, Saleh
58cc70a0-8cc3-4718-9fe4-69f1c2698bbe
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Giles, Rachel H.
cd5df71e-1002-4e89-b019-1faae24dff2d
Verhaar, Marianne C.
579ef89f-ed6f-47f8-aa53-a933e35ea089
Joles, Jaap A.
911a0118-2e68-471f-9f54-7662d77f725d
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Oosterhuis, Nynke R.
5de6affa-4f63-4694-8984-9ab10a65178d
Frenay, Anne-Roos S.
314506f7-a54f-4950-88fa-d22db328ab1d
Wesseling, Sebastiaan
add12e02-11da-4a03-835f-718ecaecc7ad
Snijder, Pauline M.
2599539b-34f7-4db3-aa91-0798f99c48a5
Slaats, Gisela G.
23d0d509-bc29-403d-a658-75f42002be7a
Yazdani, Saleh
58cc70a0-8cc3-4718-9fe4-69f1c2698bbe
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Giles, Rachel H.
cd5df71e-1002-4e89-b019-1faae24dff2d
Verhaar, Marianne C.
579ef89f-ed6f-47f8-aa53-a933e35ea089
Joles, Jaap A.
911a0118-2e68-471f-9f54-7662d77f725d
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3

Oosterhuis, Nynke R., Frenay, Anne-Roos S., Wesseling, Sebastiaan, Snijder, Pauline M., Slaats, Gisela G., Yazdani, Saleh, Fernandez, Bernadette O., Feelisch, Martin, Giles, Rachel H., Verhaar, Marianne C., Joles, Jaap A. and van Goor, Harry (2015) DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats. Nitric Oxide, 49, 56-66. (doi:10.1016/j.niox.2015.07.001). (PMID:26192363)

Record type: Article

Abstract

Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) share signaling and vasorelaxant properties and are involved in proliferation and apoptosis. Inhibiting NO production or availability induces hypertension and proteinuria, which is prevented by concomitant blockade of the H2S producing enzyme cystathionine ?-lyase (CSE) by D,L-propargylglycine (PAG). We hypothesized that blocking H2S production ameliorates Angiotensin II (AngII)-induced hypertension and renal injury in a rodent model. Effects of concomitant administration of PAG or saline were therefore studied in healthy (CON) and AngII hypertensive rats. In CON rats, PAG did not affect systolic blood pressure (SBP), but slightly increased proteinuria. In AngII rats PAG reduced SBP, proteinuria and plasma creatinine (180±12 vs. 211±19 mmHg; 66±35 vs. 346±92 mg/24h; 24±6 vs. 47±15 ?mol/L, respectively; p<0.01). Unexpectedly, kidney to body weight ratio was increased in all groups by PAG (p<0.05). Renal injury induced by AngII was reduced by PAG (p<0.001). HO-1 gene expression was increased by PAG alone (p<0.05). PAG increased inner cortical tubular cell proliferation after 1 week and decreased outer cortical tubular nucleus number/field after 4 weeks. In vitro proximal tubular cell size increased after exposure to PAG. In summary, blocking H2S production with PAG reduced SBP and renal injury in AngII infused rats. Independent of the cardiovascular and renal effects, PAG increased HO-1 gene expression and kidney weight. PAG alone increased tubular cell size and proliferation in-vivo and in-vitro. Our results are indicative of a complex interplay of gasotransmitter signaling/action of mutually compensatory nature in the kidney.

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Accepted/In Press date: 7 July 2015
e-pub ahead of print date: 17 July 2015
Published date: 15 September 2015
Keywords: hydrogen sulfide, dl-propargylglycine, angiotensin-II, proteinuria, hypertension, kidney weight
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 379522
URI: https://eprints.soton.ac.uk/id/eprint/379522
ISSN: 1089-8603
PURE UUID: 4604bae1-7d5c-4da6-9d1a-c13aef303ac5
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 03 Aug 2015 16:06
Last modified: 06 Jun 2018 12:29

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Contributors

Author: Nynke R. Oosterhuis
Author: Anne-Roos S. Frenay
Author: Sebastiaan Wesseling
Author: Pauline M. Snijder
Author: Gisela G. Slaats
Author: Saleh Yazdani
Author: Bernadette O. Fernandez
Author: Martin Feelisch ORCID iD
Author: Rachel H. Giles
Author: Marianne C. Verhaar
Author: Jaap A. Joles
Author: Harry van Goor

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