P32 Propargyl glycine increases kidney weight in different rodent models of hypertension and proteinuria

Hydrogen sulfide (H2S) and nitric oxide (NO) share signaling and vasorelaxant properties. Blocking NO induces hypertension and proteinuria. However, hypertension and proteinuria are prevented by blocking production of NO and H2S (propargyl glycine (PAG)) [Wesseling et al., Nitric oxide (2013) 31 S30–S31]. We hypothesized that blocking production of H2S ameliorates hypertension and proteinuria in other rodent models. We studied effects of concomitant PAG in rat models of hypertension and proteinuria: angiotensin II infusion (AngII) and 5/6 nephrectomy (SNX). Compared with vehicle PAG in AngII rats reduced systolic blood pressure (SBP), 179 [165–179] vs. 210 [185–239] mmHg and proteinuria 54 [20–115] vs. 329 [235–513] mg/24 h (both p < 0.01), but not in SNX rats: 161 [104–212] vs. 139 [126–195] mmHg, and 152 [11–294] vs. 79 [25–116] mg/24 h (both p > 0.1). Kidney to body weight ratio was increased in both groups by PAG compared with respective vehicle groups: 0.57 [0.48–0.64] vs. 0.48 [0.47–0.54], p < 0.05 after AngII and 0.54 [0.35–0.66] vs. 0.37 [0.23–0.44] mg/100 g in SNX, p < 0.01. In SNX this was accompanied by vacuolization of proximal tubules. Blocking H2S production with PAG in combination with various other interventions increased kidney weight independent of effects on SBP and proteinuria suggesting a renal toxic effect of PAG.