ANGIOTENSIN-II RECEPTOR SUBTYPE AT(1) AND AT(2) EXPRESSION AFTER HEART-TRANSPLANTATION

Citation
L. Gullestad et al., ANGIOTENSIN-II RECEPTOR SUBTYPE AT(1) AND AT(2) EXPRESSION AFTER HEART-TRANSPLANTATION, Cardiovascular Research, 38(2), 1998, pp. 340-347
Citations number
44
Categorie Soggetti
Cardiac & Cardiovascular System
Journal title
ISSN journal
00086363
Volume
38
Issue
2
Year of publication
1998
Pages
340 - 347
Database
ISI
SICI code
0008-6363(1998)38:2<340:ARSAAA>2.0.ZU;2-B
Abstract
Objective: Cardiac hypertrophy appears early after heart transplantati on, and may represent a myocardial response to injury. Recent evidence suggests that angiotensin II (Ang Ii) may promote growth through the AT(1) and inhibit growth through the AT(2) receptor subtypes. We there fore asked whether hypertrophy after heart transplantation is characte rized by alterations in Ang II receptor gene expression. Methods: The expression of Ang II receptor subtypes, AT(1) and AT(2), was analyzed in right ventricular endomyocardial biopsies taken from 10 human donor hearts prior to implantation (controls) and from 17 heart transplant recipients, Il studied during annual evaluation (> 1 year after transp lantation) and 6 one week after transplantation. Competitive reverse t ranscription polymerase chain reaction (RT-PCR) was performed using sy nthetic RNA internal standards for both receptor subtypes. Results: AT (1) and AT(2) receptor mRNAs were detected in all samples. AT(1) recep tor mRNA decreased 4.5 fold (p <0.01) and AT(2) receptor mRNA 4.2 fold (p < 0.001) in transplant patients compared with controls. In the sub group of patients examined one week after surgery AT(1) was reduced re lative to AT(2) receptor mRNA, resulting in an altered ratio of AT(1) to AT(2) early after transplantation, There was no correlation between Ang II receptor levels and left ventricular wall thickness, and the d ecrease in receptor level did not correlate with any hemodynamic param eters, cyclosporine blood levels, or plasma renin, Ang II or pANP, exc ept for a negative correlation between AT(2) mRNA and plasma renin (r = - 0.49,p = 0.05). Conclusions: Contrary to our expectations, mRNA fo r both Ang II receptors was downregulated after heart transplantation. The cause of myocardial hypertrophy after heart transplantation is st ill unclear, but the hypertrophy does not appear to be driven by incre ased transcription of the AT(1) receptor. (C) 1998 Elsevier Science B. V. All fights reserved.