학술논문

Portal hypertension is associated with increased mRNA levels of vasopressor G-protein-coupled receptors in human hepatic arteries.
Document Type
Article
Source
European Journal of Clinical Investigation. Mar2003, Vol. 33 Issue 3, p249-255. 7p.
Subject
*PORTAL hypertension
*MESSENGER RNA
*CELL receptors
*HEPATIC artery
Language
ISSN
0014-2972
Abstract
Abstract 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 (ETA ) and B (ETB ). 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; ETA: 4-fold, P = 0·02; ETB: 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. [ABSTRACT FROM AUTHOR]