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

Oosterhuis, N. R., Frenay, A-R. S., Wesseling, S., Snijder, P. M., Slaats, G. G., Yazdani, S., Fernandez, B. O., Feelisch, M., Giles, R. H., Verhaar, M. C., Joles, J. A. & van Goor, H., 15-Sep-2015, In : Nitric oxide-Biology and chemistry. 49, p. 56-66 11 p.

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  • DL-propargylglycine reduces blood pressure and renal injury but increases kidney

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DOI

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

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 gamma-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/24 h; 24 +/- 6 vs. 47 15 mu 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 AnglI 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. (C) 2015 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)56-66
Number of pages11
JournalNitric oxide-Biology and chemistry
Volume49
Publication statusPublished - 15-Sep-2015

    Keywords

  • Hydrogen sulfide, DL-Propargylglycine, Angiotensin-II, Proteinuria, Hypertension, Kidney weight, CYSTATHIONINE-GAMMA-LYASE, ENDOGENOUS HYDROGEN-SULFIDE, SMOOTH-MUSCLE-CELLS, NITRIC-OXIDE, HEME OXYGENASE-1, CARBON-MONOXIDE, INDUCED HYPERTENSION, OXIDATIVE STRESS, IN-VIVO, EXPRESSION

ID: 23044550