CHARACTERIZATION OF LYMPHOCYTE BETA-ADRENOCEPTOR ACTIVITY AND G(S)-PROTEIN IN PATIENTS WITH RHEUMATIC HEART VALVULAR DISEASE

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.