Sunga P S, Rabkin S W
Department of Medicine, University Hospital Research Centre, University of British Columbia, Vancouver, Canada.
Cardiovasc Res. 1991 Nov;25(11):965-8. doi: 10.1093/cvr/25.11.965.
The aim was to examine the effect of angiotensin II on the response of hypertrophic cardiac myocytes to the beta adrenergic receptor agonist isoprenaline.
Viable ventricular myocytes were isolated from hypertrophic hearts of Dahl S rats and hearts of Dahl R rats. Myocytes were stimulated with isoprenaline. cAMP content was measured by competitive binding radioimmunoassay.
Hypertrophic Dahl S myocytes had smaller cAMP response to isoprenaline than Dahl R myocytes (p less than 0.05). Angiotensin II inhibited cAMP stimulation in Dahl R myocytes. In contrast, angiotensin II increased cAMP accumulation in hypertrophic Dahl S myocytes compared to the effect of isoprenaline alone (p less than 0.05). Enhancement of isoprenaline stimulation of cAMP accumulation by angiotensin II was positively related to the degree of cardiac hypertrophy. Angiotensin II treatment in the absence of isoprenaline had no effect on cAMP levels.
The reversal of the normal inhibitory action of angiotensin II is evidence of a unique alteration in the signal transduction of beta receptor stimulation and is of potential importance in defining the role of angiotensin II in cardiac hypertrophy.
旨在研究血管紧张素II对肥厚心肌细胞对β肾上腺素能受体激动剂异丙肾上腺素反应的影响。
从Dahl S大鼠的肥厚心脏和Dahl R大鼠的心脏中分离出有活力的心室肌细胞。用异丙肾上腺素刺激肌细胞。通过竞争性结合放射免疫分析法测量环磷酸腺苷(cAMP)含量。
肥厚的Dahl S肌细胞对异丙肾上腺素的cAMP反应比Dahl R肌细胞小(p<0.05)。血管紧张素II抑制Dahl R肌细胞中的cAMP刺激。相反,与单独使用异丙肾上腺素相比,血管紧张素II增加了肥厚的Dahl S肌细胞中的cAMP积累(p<0.05)。血管紧张素II对异丙肾上腺素刺激cAMP积累的增强作用与心脏肥大程度呈正相关。在没有异丙肾上腺素的情况下,血管紧张素II处理对cAMP水平没有影响。
血管紧张素II正常抑制作用的逆转证明了β受体刺激信号转导中的独特改变,并且在确定血管紧张素II在心脏肥大中的作用方面具有潜在重要性。