Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure

• Published in: Journal of the American College of Cardiology Vol. 40; no. 1; pp. 119 - 125
• Main Authors: Kuoppala, Antti, Shiota, Naotaka, Kokkonen, Jorma O, Liesmaa, Inka, Kostner, Karam, Mäyränpää, Mikko, Kovanen, Petri T, Lindstedt, Ken A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 03.07.2002; Elsevier Science; Elsevier Limited
• Subjects: ACE inhibitors; Adult; Biological and medical sciences; Blotting, Western; Cardiology; Cardiology. Vascular system; Cardiomyopathy; Cardiomyopathy, Dilated - metabolism; Cardiovascular disease; Coronary Disease - metabolism; Deoxyribonucleic acid; DNA; Down-Regulation; Enzymes; Female; Heart; Heart failure; Heart Failure - etiology; Heart Failure - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Male; Medical sciences; Middle Aged; Myocardium - metabolism; Nitric oxide; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type III; Pathogenesis; Patients; Polymerase chain reaction; Receptor, Bradykinin B2; Receptors, Bradykinin - genetics; Receptors, Bradykinin - metabolism; Receptors, Bradykinin - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Smooth muscle; Ventricular Function, Left - physiology; Austria; Finland; AT-2R; BK-2R; AT-1R; eNOS; ACE; RNA; BK; IDC; HCAEC; DNA; RT-PCR; GAPDH; CHD; HF; PCR; LVH; Human; Heart failure; Pathophysiology; Enzyme; Pathogenesis; Cardiovascular disease; Exploration; Terminal stage; B2 bradykinin receptor; Nitric-oxide synthase; Left ventricle; Endothelium; Regulation(control); Heart disease; Oxidoreductases
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(02)01928-9

We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF). Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein. In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein–coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts. These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.