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Portal hypertension is associated with increased mRNA levels of vasopressor G‐protein‐coupled receptors in human hepatic arteries
Author(s) -
Neef M.,
Biecker E.,
Heller J.,
Schepke M.,
Nischalke H. D.,
Wolff M.,
Spengler U.,
Reichen J.,
Sauerbruch T.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01131.x
Subject(s) - receptor , medicine , endocrinology , vasopressin , angiotensin ii , endothelin receptor , portal hypertension , cirrhosis , angiotensin ii receptor type 1 , messenger rna , biology , biochemistry , gene
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: α1 adrenoceptor (AR) subtypes a, b and d, angiotensin II type 1 receptor (AT1), arginine vasopressin receptor type 1a (V1a), endothelin receptor type A (ET A ) and B (ET B ). Materials and 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 α1aAR 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 (α1bAR: 4‐fold, P = 0·013; AT1: 16‐fold, P = 0·024; V1a: 23‐fold, P = 0·001; ET A : 4‐fold, P = 0·02; ET B : 8‐fold, P = 0·008). No mRNA for the α1dAR was detected either in the donor or recipient hepatic arteries. Conclusion 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.