Vaka 2017 Hypertension

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Abstract P265: Placental ischemia causes renal mitochondrial impairment in reduced uterine perfusion pressure rats.

Link: Open Access

Vaka VR, McMaster KM, Cunningham MW, Ibrahim T, Amaral LM, Usry NE, LaMarca B (2017)


Preeclampsia (PE) is characterized by new onset hypertension in pregnancy and is associated with renal dysfunction, proteinuria and is believed to be initiated by placental ischemia. Mitochondrial dysfunction is an important source of reactive oxygen species (ROS) generation. To better understand the role of mitochondrial dysfunction in hypertension during PE we examined renal mitochondrial expression in the kidney of RUPP rats.

Female Sprague Dawley rats were dived into two groups; normal pregnant (NP) and RUPP rats. On gestational day (GD) 14, RUPP surgery was performed, GD18 carotid catheters were inserted, and GD19 conscious blood pressure (MAP) was measured, renal mitochondria were isolated for respiration and analysis. Respiration measurements were performed on intact isolated mitochondria under glutamate/malate as complex I substrate using Oroboros Oxygraph-2K. Oxidative phosphorylation was analyzed by western blot using total Oxphos cocktail antibody and VDAC.

MAP was elevated in RUPP (n=8) vs NP rats (n=10) (125±6 vs. 99±2 mmHg, p<0.05). RUPP (n=3) renal mitochondria show reduced expression of Complex I (0.5±0.02 vs 0.8±0.09, p<0.05) and Complex II (0.7±0.03 vs 1±0.08, p<0.05) compared to NP mitochondria. State 3 (624±112 vs 878±9 pmol/sec/mg, p=0.22) and maximal (496±87vs 748±75 pmol/sec/mg, p=0.14) respiration rates trended towards reduction in RUPPs (n=4) compared to NP (n=2).

Reduced expression of Complex I and II expression with reduced respiratory rates indicate mitochondrial impairment in the RUPP kidneys. Although, renal mitochondrial mediated oxidative stress may be one mechanism of hypertension in the RUPP rat model of PE, further exploration of oxidative stress in the kidney is necessary to fully understand the contribution of mitochondrial mediated oxidative stress to pathology of PE.

Bioblast editor: Kandolf G

Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Kidney, Genital  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase 

Coupling state: OXPHOS  Pathway: N, S  HRR: Oxygraph-2k