Hohl C M, Hu B, Fertel R H, Russell J C, McCune S A, Altschuld R A
Ohio State University, Columbus 43210-1218.
Cardiovasc Res. 1993 Feb;27(2):238-42. doi: 10.1093/cvr/27.2.238.
The aim was to compare beta adrenergic receptors, cAMP production, and Ca2+ accumulation by the sarcoplasmic reticulum in ventricular cardiomyocytes from female SHHF/Mcc-cp and JCR:LA-cp rats. Whereas rats from both strains exhibit gross obesity when the animals are homozygous for the recessive "corpulent" gene, the SHHF rats, which are hypertensive, all develop heart failure during their second year of life. The normotensive JCR:LA-cp animals do not.
beta Adrenergic receptor number, ligand affinity, isoprenaline and forskolin stimulated cyclic AMP production, and ATP dependent, phosphate supported 45Ca2+ uptake by the sarcoplasmic reticulum were compared in ventricular cardiomyocytes isolated from 6 months old obese female SHHF/Mcc-cp and obese and lean female JCR:LA-cp rats.
Bmax and Kd for (-)-[125iodo]-cyanopindolol (125ICYP) binding were each approximately 50% lower in SHHF/Mcc-cp v JCR:LA-cp myocytes. Cyclic AMP production in response to isoprenaline, isoprenaline plus isobutylmethylxanthine (IBMX), and forskolin plus IBMX was also significantly depressed in the SHHF/Mcc-cp cells. In addition, sarcoplasmic reticular 45Ca2+ uptake by SHHF/Mcc-cp cells was 35% lower than in lean or obese JCR:LA-cp myocytes. Isoprenaline stimulated cAMP production and sarcoplasmic reticular Ca2+ uptake by the lean JCR:LA-cp cells were comparable to that described previously for myocytes from normal Sprague-Dawley rats. By contrast, Bmax and Kd for 125ICYP binding by the JCR myocytes differed substantially from previously described results for normal Sprague-Dawley rats, whereas values for the SHHF cells did not.
Declines in Ca sequestration by the sarcoplasmic reticulum of ventricular cardiomyocytes from obese, hypertensive SHHF rats are not related to their obesity. However, obesity may contribute to the decline in cAMP production. This may account, in part, for the exacerbation by obesity of cardiac dysfunction in essential hypertension.
比较雌性SHHF/Mcc-cp大鼠和JCR:LA-cp大鼠心室心肌细胞中的β肾上腺素能受体、环磷酸腺苷（cAMP）生成以及肌浆网对钙离子的摄取。当这两种品系的大鼠对于隐性“肥胖”基因呈纯合状态时都会出现明显肥胖，但SHHF大鼠患有高血压，在其生命的第二年都会发展为心力衰竭。血压正常的JCR:LA-cp动物则不会。
比较从6个月大的肥胖雌性SHHF/Mcc-cp大鼠以及肥胖和瘦的雌性JCR:LA-cp大鼠分离出的心室心肌细胞中β肾上腺素能受体数量、配体亲和力、异丙肾上腺素和福斯高林刺激的环磷酸腺苷生成，以及肌浆网对依赖三磷酸腺苷（ATP）、由磷酸盐支持的45钙离子的摄取。
与JCR:LA-cp心肌细胞相比，SHHF/Mcc-cp心肌细胞中（-）-[125碘]-氰基吲哚洛尔（125ICYP）结合的最大结合容量（Bmax）和平衡解离常数（Kd）各自约低50%。SHHF/Mcc-cp细胞中对异丙肾上腺素、异丙肾上腺素加异丁基甲基黄嘌呤（IBMX）以及福斯高林加IBMX的环磷酸腺苷生成反应也显著降低。此外，SHHF/Mcc-cp细胞的肌浆网对45钙离子的摄取比瘦的或肥胖的JCR:LA-cp心肌细胞低35%。瘦的JCR:LA-cp细胞中异丙肾上腺素刺激的环磷酸腺苷生成和肌浆网对钙离子的摄取与先前描述的正常斯普拉格-道利大鼠心肌细胞的情况相当。相比之下，JCR心肌细胞中125ICYP结合的Bmax和Kd与先前描述的正常斯普拉格-道利大鼠的结果有很大差异，而SHHF细胞的值则没有。
肥胖、高血压的SHHF大鼠心室心肌细胞的肌浆网对钙离子的摄取减少与其肥胖无关。然而，肥胖可能导致环磷酸腺苷生成减少。这可能部分解释了肥胖会加剧原发性高血压患者的心脏功能障碍。
