PMID- 24733030
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20140702
IS  - 1473-5598 (Electronic)
IS  - 0263-6352 (Linking)
VI  - 32
IP  - 7
DP  - 2014 Jul
TI  - Coagulation factor XIIa-kinin-mediated contribution to hypertension of chronic 
      kidney disease.
PG  - 1523-33; discussion 1533
LID - 10.1097/HJH.0000000000000192 [doi]
AB  - BACKGROUND: Activated coagulation Factor XII (FXIIa) infusion increases 
      peripheral resistance (TPR) and mean arterial pressure (MAP) of Brown Norway but 
      not plasma kininogen deficient Brown Norway Katholiek (BNK) rats. FXIIa 
      concentrations are elevated in hypertensive end-stage renal disease patients 
      receiving conventional haemodialysis (CHD). Conversion to nocturnal haemodialysis 
      (NHD) lowers peripheral resistance and MAP. OBJECTIVE: To determine whether the 
      plasma coagulation FXIIa-kallikrein-kinin axis contributes to the hypertension of 
      chronic kidney disease (CKD). METHODS: Plasma FXIIa and haemodynamic data were 
      acquired in 11 CHD patients before and after 2 months of NHD. Cardiac and 
      systemic haemodynamics of Brown Norway and BNK rats rendered hypertensive and 
      uremic by 5/6 nephrectomy (NX) were determined before and after acute FXIIa 
      inhibition. RESULTS: FXIIa was increased three-fold in CHD patients relative to 
      control plasma (P < 0.05). After conversion to NHD, both DeltaMAP and DeltaTPR correlated 
      with DeltaFXIIa. In rats, plasma FXIIa was three-fold higher in both NX groups than 
      respective SHAM controls (all P < 0.05), but MAP (147 +/- 4 vs. 133 +/- 2 mmHg; P < 
      0.05) and TPR (2.8 +/- 0.2 vs. 2.3 +/- 0.2 units; P < 0.05) were greater in Brown 
      Norway NX (n = 16) than in BNK (n = 15) NX rats. FXIIa correlated with MAP only 
      in Brown Norway NX, and plasma catecholamines were increased relative to SHAM 
      only in Brown Norway NX (P < 0.05). In Brown Norway NX rats, FXIIa inhibitor 
      infusion decreased MAP (-12 mmHg) and TPR (-0.5 Units) (both P < 0.05), and 
      halved catecholamines (P < 0.05). No such changes occurred in BNK NX rats. 
      CONCLUSION: FXIIa-kininogen mediated vasoconstriction contributes significantly 
      to CKD hypertension in Brown Norway rats; this novel mechanism may be active in 
      humans with CKD.
FAU - Papageorgiou, Peter C
AU  - Papageorgiou PC
AD  - aHeart and Stroke/Richard Lewar Centre of Excellence bDepartment of Medicine, 
      University Health Network and Mount Sinai Hospital cDepartment of Physiology, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Chan, Christopher T
AU  - Chan CT
FAU - Yeo, Erik L
AU  - Yeo EL
FAU - Backx, Peter H
AU  - Backx PH
FAU - Floras, John S
AU  - Floras JS
LA  - eng
GR  - MOP53284/Canadian Institutes of Health Research/Canada
GR  - MOP62954/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Kinins)
RN  - EC 3.4.21.38 (Factor XIIa)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Blood Pressure/physiology
MH  - Disease Models, Animal
MH  - Factor XIIa/*metabolism
MH  - Female
MH  - Humans
MH  - Hypertension, Renal/*blood/*etiology/physiopathology
MH  - Kidney Failure, Chronic/*blood/*complications/physiopathology
MH  - Kinins/*blood
MH  - Male
MH  - Middle Aged
MH  - Rats
MH  - Rats, Inbred BN
MH  - Renal Dialysis
MH  - Vascular Resistance/physiology
MH  - Vasoconstriction/physiology
EDAT- 2014/04/16 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/04/16 06:00
PHST- 2014/04/16 06:00 [entrez]
PHST- 2014/04/16 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - 10.1097/HJH.0000000000000192 [doi]
PST - ppublish
SO  - J Hypertens. 2014 Jul;32(7):1523-33; discussion 1533. doi: 
      10.1097/HJH.0000000000000192.