Portal hypertension is associated with increased mRNA levels of vasopressor G-protein-coupled receptors in human hepatic arteries.
BACKGROUND
The contractile response of human splanchnic vessels to different vasoconstrictors is attenuated in cirrhosis. Functional studies indicate a cellular signalling defect upstream of the G-protein level. The aim of the present study was to analyze expression and mRNA levels of the following most relevant vasopressor receptors in the smooth musculature of human hepatic arteries: alpha1 adrenoceptor (AR) subtypes a, b and d, angiotensin II type 1 receptor (AT1), arginine vasopressin receptor type 1a (V1a), endothelin receptor type A (ETA) and B (ETB).


METHODS
Hepatic arteries were collected from 10 donors (noncirrhotic) and 14 recipients (cirrhotic) at liver transplantations. Real-time-PCR was performed to quantify steady-state levels of receptor mRNAs.


RESULTS
alpha 1aAR mRNA levels showed no significant difference between the cirrhotic arteries and the controls while the mRNA levels of the other vasoactive receptors were significantly higher in the cirrhotic hepatic arteries (alpha 1bAR: 4-fold, P = 0.013; AT1: 16-fold, P = 0.024; V1a: 23-fold, P = 0.001; ETA: 4-fold, P = 0.02; ETB: 8-fold, P = 0.008). No mRNA for the alpha 1dAR was detected either in the donor or recipient hepatic arteries.


CONCLUSIONS
We conclude that vascular hyporeactivity to the most relevant endogenous vasoconstrictors of cirrhotic hepatic arteries is not caused by a receptor down-regulation at mRNA levels. In contrast they were up-regulated.
Neef
M
M
Department of Internal Medicine I, University of Bonn, Bonn, Germany. m.neef@uni-bonn.de
Biecker
E
E
Heller
J
J
Schepke
M
M
Nischalke
H D
HD
Wolff
M
M
Spengler
U
U
Reichen
J
J
Sauerbruch
T
T
D000328:Adult; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism*; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D017483:Receptors, Vasopressin