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

• Published in: Nitric oxide 2015-09, Vol.49, p.56-66
• Main Authors: 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., van Goor, Harry
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - metabolism; Alkynes - administration & dosage; Alkynes - pharmacology; Angiotensin II - adverse effects; Angiotensin-II; Animals; Blood Pressure - drug effects; Cell Proliferation; DL-Propargylglycine; Glycine - administration & dosage; Glycine - analogs & derivatives; Glycine - pharmacology; Heme Oxygenase-1 - metabolism; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Hypertension; Kidney - drug effects; Kidney - pathology; Kidney weight; Male; Nitric Oxide; Organ Size; Proteinuria; Rats; Rats, Sprague-Dawley
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2015.07.001

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 γ-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 μmol/L, respectively; p