ANGIOTENSIN II-RECEPTOR SUBTYPES IN HUMAN ATRIA AND EVIDENCE FOR ALTERATIONS IN PATIENTS WITH CARDIAC DYSFUNCTION

Angiotensin II (AII) has been implicated as an important factor in the pathophysiology of heart diseases. Following the recent identificatio n of two subtypes of the AII receptor in cardiac tissue of animals, we investigated the possible occurrence of these, or similar, subtypes i n human atrial tissue. In right-atrial tissue from patients undergoing heart surgery, we determined the AII-receptor profile in receptor bin ding studies, using [I-125]-angiotensin as radioligand and AII as well as two compounds selective for the receptor subtypes to identify and quantify AII-receptor subpopulations. In 35 patients (23 requiring cor onary bypasses, 10 valvular surgery and two combined coronary and valv ular surgery), the left-ventricular ejection fraction was determined i n the preoperative phase, and right- and left-atrial pressure during s urgery. In membranes of human right atria, AII receptors are present i n high density (median: B-max=294 fmol.mg(-1) protein, range: 111-2073 ) and two different subtypes can be distinguished. Type-1 receptors (A T(1)) accounted for 33+/-10% of the population whereas type-2 receptor s (AT(2)) made up 67+/-10% of the population. There was no correlation between any of the measured cardiac functions and total AII-receptor density or receptor affinity. However, the percentage of AT(1) recepto rs was higher in the atria of patients with normal right-atrial pressu re; left-ventricular ejection fraction was positively and right-atrial pressure inversely correlated with the percentage of AT(1) receptors (r=0 . 740 and -0 . 901, respectively; P<0 . 001, for bath). Moreover, the percentage of AT(2) receptors was directly correlated with the le vels of left-atrial pressure (r=0 . 853; P<0 . 001). It is concluded t hat the ratio of AT(1) to AT(2) receptors correlates well with right-a trial pressure and left-ventricular function. This is a first indicati on of a possible involvement of AII-receptor subtypes in the pathophys iology of cardiac dysfunctions.