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Plasma coagulation FXIIa levels in the 5/6 NX animal model of chronic renal failure parallel the development of hypertension
Author(s) -
Papageorgiou Peter C,
Backx Peter H,
Chan Christopher T,
Floras John S
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a897-b
In a rat bioassay model, injection of activated coagulation Factor XII (FXIIa) acutely elevates blood pressure (BP) and total peripheral resistance (TPR). In nephrectomized patients on hemodialysis, plasma FXIIa levels were elevated and tracked peri‐dialytic BP and fluid status. To test the hypothesis that FXIIa exerts a vasoconstrictor pro‐hypertensive action in chronic renal failure (CRF), BP was measured weekly by non‐invasive tail plethysmography in renal mass reduced CRF Brown Norway rats (5/6NX, n=7) and sham controls (BN, n=7) fed a low salt diet and water ad libitum . After hypertension and uremia were established, BP and hemodynamics were measured invasively using a conductance catheter (SciSense, Canada). Systolic BP was higher in the 5/6NX group compared to BN controls (173±16 vs. 120±3 mmHg; p<0.01). Heart rate, stroke volume and cardiac output were similar while TPR was 3‐fold higher (0.037±0.013 vs. 0.011±0.001 mmHg·min/RVU; p<0.03) in the 5/6NX group. FXIIa was measured using an ELISA recognising rat FXIIa developed using a novel mAb (Axis‐Shield Diagnostics,UK). FXIIa in uremic 5/6NX rats was 2‐fold higher than in controls (0.83±0.06 vs. 0.40±0.06 OD 550 ; p<0.01) and correlated with MAP ( r =0.66, p=0.01) and TPR ( r =0.61, p=0.02). These parallel changes are consistent with the concept that increases in FXIIa may contribute to hypertension in the uremic CRF rat by increasing peripheral resistance. Supported by the Canadian Institutes of Health Research and the Heart & Stroke Foundation of Canada.