DECREASED EXPRESSION OF VENTRICULAR ANGIOTENSIN RECEPTOR-TYPE-1 MESSENGER-RNA AFTER HUMAN HEART-TRANSPLANTATION

Myocardial angiotensin receptors of type 1 (AT1) are downregulated at the protein and mRNA levels in human heart failure. No data are availa ble for the transplanted human heart, which frequently exhibits functi onal alterations. The aim of the present study was the quantitation of ventricular AT1 mRNA content in endomyocardial biopsies from patients after heart transplantation. For the determination of AT1 mRNA we use d a novel quantitative reverse transcription polymerase chain reaction with low variance (6%) based on an internal AT1 cRNA standard, liquid -phase hybridization of polymerase chain reaction products in microtit er plates, and quantitation by enzyme-linked immunosorbent assay. Righ t ventricular biopsies from 16 patients after heart transplantation (l eft ventricular ejection fraction 67+/-7%) were compared with 12 patie nts with normal cardiac function (left ventricular ejection fraction 6 2+/-5%). A 46% lower AT1 mRNA content was found in biopsies from the 1 6 patients after heart transplantation than in the 12 controls (heart transplantation, 200+/-25 AT1 mRNA copies/ng RNA; controls, 368+/-50; P<0.01). When AT1 mRNA content was related to the stably expressed GAP DH mRNA, a 49% decrease was detected (AT1/GAPDH: patients, 2.4+/-0.25; controls, 4.7+/-0.6; P<0.006). No association between the extent of A T1 downregulation and clinical or hemodynamic variables was detected. In the human heart ventricular AT1 is downregulated after orthotopic h eart transplantation. The decrease in AT1 mRNA is not associated with altered systolic function. This may partially reflect a loss of autono mic nerves and thus altered nervous control of the heart.