Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction

Angiotensin II (All) has been implicated as an important factorin the pathophysiology of heart diseases. Following the recentidentification of two subtypes of the All receptor in cardiactissue of animals, we investigated the possible occurrence ofthese, or similar, subtypes in human atrial tissue. In right-atrialtissue from patients undergoing heart surgery, we determinedthe All-receptor profile in receptor binding studies, using[¹²⁵I]-angiotensin as radioligand and All as well as two compoundsselective for the receptor subtypes to identify and quantifyAll-receptor subpopulations. In 35 patients (23 requiring coronarybypasses, 10 vaivular surgery and two combined coronary andvalvular surgery), the left-ventricular ejection fraction wasdetermined in the preoperative phase, and right- and left-atrialpressure during surgery. In membranes of human right atria,All receptors are present in high density (median: B_max= 294fmol. mg^–1 protein, range: 111-2073) and two differentsubtypes can be distinguished. Type-1 receptors (AT₁) accountedfor 33 ± l0% of the population whereas type-2 receptors(AT₂) made up 67 ± 10% of the population. There was nocorrelation between any of the measured cardiac functions andtotal All-receptor density or receptor affinity. However, thepercentage of AT₁ receptors was higher in the atria of patientswith normal right-atrial pressure; left-ventricular ejectionfraction was positively and right-atrial pressure inverselycorrelated with the percentage of AT₁ receptors (r=0·740and -0·901, respectively; P<0·001, for both).Moreover, the percentage of AT receptors was directly correlatedwith the levels of left-atrial pressure (r=0·853; P<0·001).It is concluded that the ratio of AT₁ to AT₂ receptors correlateswell with right-atrial pressure and left-ventricular function.This is a first indication of a possible involvement of All-receptorsubtypes in the pathophysiology of cardiac dysfunctions.