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 identification of two subtypes of the AII receptor in cardiac tissue of animals, we investigated the possible occurrence of these, or similar, subtypes in human atrial tissue. In right-atrial tissue from patients undergoing heart surgery, we determined the AII-receptor profile in receptor binding studies, using [125I]-angiotensin as radioligand and subtypes to identify and quantify AII-receptor subpopulations. In 35 patients (23 requiring coronary bypasses, 10 valvular surgery and two combined coronary and valvular surgery), the left-ventricular ejection fraction was determined in the preoperative phase, and right- and left-atrial pressure during surgery. In membranes of human right atria, AII receptors are present in high density (median: Bmax = 294 fmol.mg-1 protein, range: 111-2073) and two different subtypes can be distinguished. Type-1 receptors (AT1) accounted for 33 +/- 10% of the population whereas type-2 receptors (AT2) 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 AT1 receptors was higher in the atria of patients with normal right-atrial pressure; left-ventricular ejection fraction was positively and right-atrial pressure inversely correlated with the percentage of AT1 receptors (r = 0.740 and -0.901, respectively; P < 0.001, for both). Moreover, the percentage of AT2 receptors was directly correlated with the levels of left-atrial pressure (r = 0.853; P < 0.001). It is concluded that the ratio of AT1 to AT2 receptors correlates well with right-atrial pressure and left-ventricular function. This is a first indication of a possible involvement of AII-receptor subtypes in the pathophysiology of cardiac dysfunctions.
Rogg
H
H
Research Department, Ciba-Geigy Limited, Basel, Switzerland.
de Gasparo
M
M
Graedel
E
E
Stulz
P
P
Burkart
F
F
Eberhard
M
M
Erne
P
P
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000032:analysis*; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000503:physiopathology; D046508:Culture Techniques; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011945:Receptors, Angiotensin / Q000032:analysis*
D011945:Receptors, Angiotensin; D000804:Angiotensin II