N. Dzimiri et al., CHARACTERIZATION OF LYMPHOCYTE BETA-ADRENOCEPTOR ACTIVITY AND G(S)-PROTEIN IN PATIENTS WITH RHEUMATIC HEART VALVULAR DISEASE, Fundamental and clinical pharmacology, 9(4), 1995, pp. 372-380
In order to test whether the beta-adrenoceptor activity in rheumatic h
eart valvular disease depends on the ventricular load conditions, we d
etermined their density and binding affinity to [I-125]-iodocyanopindo
lol in lymphocytes, as well as plasma catecholamine and cAMP levels in
69 patients with regurgitant and stenotic lesions of the aortic and m
itral valves. The patients were classified as having left ventricular
pressure overload (LVP), left ventricular volume overload (LVV), mixed
lesions (MOL) or right ventricular pressure overload (RVP). The beta-
adrenoceptor activity was determined by radioligand binding methods, c
atecholamines by high performance liquid chromatography using an elect
rochemical detector and cAMP by radioimmunoassay. The mean beta-adreno
ceptor density (B-max) of the control group was 60.1 +/- 9.5 integral
mol (n = 29) per 10(6) lymphocytes. In the study population, the densi
ty was decreased by 83% in LVP, 78% in LVV, 87% in MOL and 86% in RVP.
Plasma norepinephrine was elevated by 89% in LVP and 60% in MOL, epin
ephrine by 43% in LVP, 50% in VOL, 115% in MOL and 20% in RVP, while d
opamine was not significantly changed, and cAMP was slightly elevated
in all four groups. Screening for activating mutational changes in the
G(s alpha)-protein gave negative results, possibly dissociating the e
levation in plasma cAMP from stimulatory effects of such abnormalities
in the G(s)-protein signaling. These results show a significant atten
uation in lymphocyte beta-adrenoceptor density of patients with rheuma
tic heart valvular disease, irrespective of the type of the prevailing
ventricular load conditions. The reduction in receptor density is acc
ompanied by a significant increase in plasma norepinephrine levels in
patients with a left ventricular pressure overload and epinephrine in
those with volume overload.