Dzimiri N, Moorji A, Kumar M, Bakr S, Kumar N, Almotrefi A A, Halees Z
Department of Cardiovascular Diseases, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Gen Pharmacol. 1996 Apr;27(3):539-43. doi: 10.1016/0306-3623(95)02030-6.
We have investigated the possibility that the various left ventricular load conditions may exert different effects on the sympathetic function by comparing the influence of volume (VOL) and pressure (POL) overload on platelet alpha-adrenoceptor activity, plasma catecholamines and cAMP in 44 patients with rheumatic heart valvular disease. Receptor activity was determined by radioligand binding methods, catecholamines by HPLC using an electrochemical detector, and cAMP by radioimmunoassay. The mean alpha-adrenoceptor density (Bmax) of the control group (n = 29) was 4.71 +/- 0.41 fmol per 10(7) platelets and the corresponding dissociation constant (Kd) was 2.47 +/- 0.15 nM. In VOL patients, the density was elevated by 70% (P < 0.0001), but it remained unchanged in the POL patients. In contrast to the Bmax, the Kd of the VOL group was not changed, and it increased by 34% (P < 0.01) in the POL group. Norepinephrine was elevated by 91% (P < 0.05) in POL, and epinephrine increased by 65% (P < 0.05) in POL and 71% (P < 0.05) in VOL. These results suggest that the sympathetic nervous system responds to left ventricular volume overload by increasing alpha-adrenoceptor density with no apparent change in receptor affinity toward [3H]-yohimbine binding, and to left ventricular pressure overload by decreasing their binding affinity without a parallel decrease in receptor density. The increase in receptor density in VOL is accompanied by an increase in plasma epinephrine, and the decrease in binding affinity in POL is associated with increased plasma norepinephrine and epinephrine levels.
我们通过比较44例风湿性心脏瓣膜病患者容量（VOL）和压力（POL）超负荷对血小板α-肾上腺素能受体活性、血浆儿茶酚胺和环磷酸腺苷（cAMP）的影响，研究了各种左心室负荷情况对交感神经功能可能产生不同影响的可能性。受体活性采用放射性配体结合法测定，儿茶酚胺采用高效液相色谱法（HPLC）并用电化学检测器检测，cAMP采用放射免疫分析法测定。对照组（n = 29）的平均α-肾上腺素能受体密度（Bmax）为每10⁷个血小板4.71±0.41 fmol，相应的解离常数（Kd）为2.47±0.15 nM。在VOL患者中，受体密度升高了70%（P < 0.0001），但在POL患者中保持不变。与Bmax不同，VOL组的Kd没有变化，而POL组的Kd增加了34%（P < 0.01）。去甲肾上腺素在POL组升高了91%（P < 0.05），肾上腺素在POL组升高了65%（P < 0.05），在VOL组升高了71%（P < 0.05）。这些结果表明，交感神经系统对左心室容量超负荷的反应是增加α-肾上腺素能受体密度，而受体对[³H]-育亨宾结合的亲和力无明显变化；对左心室压力超负荷的反应是降低其结合亲和力，而受体密度没有相应降低。VOL组受体密度的增加伴随着血浆肾上腺素的增加，POL组结合亲和力的降低与血浆去甲肾上腺素和肾上腺素水平的升高有关。
