CHARACTERIZATION AND LOCALIZATION OF ENDOTHELIN RECEPTOR SUBTYPES IN THE HUMAN ATRIOVENTRICULAR CONDUCTING SYSTEM AND MYOCARDIUM

The characterization and localization of endothelin A (ET(A)) and endothelin B (ET(B)) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ET(A) (BQ123) and ET(B) (BQ3020) compounds in conjunction with [I-125]endothelin-1 revealed the presence of ET(A) and ET(B) receptors in the left ventricular free wall (BQ123: 57+/-5% ET(A) 43+/-2% ET(B), n=3; BQ3020: 67+/-3% ET(A), 33+/-3% ET(B), n=3). Autoradiography using [I-125]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ET(A) and ET(B) receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ET(B) receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding interventricular and interatrial septa (p<0.0001). There was a lower density of ET(B) receptors in the interventricular septum compared with the interatrial septum and the atrioventricular conducting system (p=0.009) and a lower density of ET(A) receptors in the atrioventricular conducting system compared with interatrial and interventricular septa (p=0.008). Isolated right atrial myocytes showed a higher proportion of ET(A) receptors (91+/-12%, n=3). Amplification of left ventricular free wall cDNA by polymerase chain reaction revealed the presence of ET(A) and ET(B) receptor mRNA. mRNA for both subtypes was detected in isolated atrial myocytes. In situ hybridization showed ET(A) and ET(B) receptor mRNA localization to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. These studies demonstrate the presence of ET(A) and ET(B) receptors in human myocardium and the atrioventricular conducting system.