EFFECT OF LEFT-VENTRICULAR PRESSURE AND VOLUME OVERLOAD ON ALPHA-ADRENOCEPTOR ACTIVITY IN PATIENTS WITH RHEUMATIC HEART VALVULAR DISEASE

We have investigated the possibility that the various left ventricular load conditions may exert different effects on the sympathetic functi on by comparing the influence of volume (VOL) and pressure (POL) overl oad on platelet a adrenoceptor activity, plasma catecholamines and cAM P in 44 patients with rheumatic heart valvular disease. Receptor activ ity was determined by radioligand binding methods, catecholamines by H PLC using an electrochemical detector, and cAMP by radioimmunoassay. T he mean a adrenoceptor density (B-max) of the control group (n = 29) w as 4.71 +/- 0.41 fmol per 10(7) platelets and the corresponding dissoc iation constant (K-d) was 2.47 +/- 0.15 nM. In VOL patients, the densi ty was elevated by 70% (P < 0.001), but it remained unchanged in the P OL patients. In contrast to the B,,, the K-d of the VOL group was not changed, and it increased by 34% (P < 0.01) in the POL group. Norepine phrine was elevated by 91% (P < 0.05) in POL, and epinephrine increase d by 65% (P < 0.05) in POL and 71% (P < 0.05) in VOL. These results su ggest that the sympathetic nervous system responds to left ventricular volume overload by increasing a adrenoceptor density with no apparent change in receptor affinity toward [H-3]-yohimbine binding, and to le ft ventricular pressure overload by decreasing their binding affinity without a parallel decrease in receptor density, The increase in. rece ptor density in VOL is accompanied by an increase in plasma epinephrin e, and the decrease in binding affinity in POL is associated with incr eased plasma norepinephrine and epinephrine levels.