Dumont M, Sabourin L, Lemaire S
Department of Pharmacology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
Neuropeptides. 1990 Jan;15(1):43-8. doi: 10.1016/0143-4179(90)90159-v.
In order to investigate the pathophysiological role of heart dynorphin-A (Dyn-A) in genetic hypertension, immunoreactive (ir)-Dyn-A was measured in heart extracts of spontaneously hypertensive rats (SHR) and compared with that of age matched Wistar (WR) and Wistar Kyoto (WKY) rats. Heart ir-Dyn-A contents in 8 week-old WK (84 fmol/g tissue) were not significantly different from those of age matched WKY (109 fmol/g tissue). In control WKY, the levels of ir-Dyn-A did not significantly vary with the age (from 109 to 117 fmol/g) except in 16 week-old animals which displayed a significant increase (238 fmol/g tissue) compared to younger animals. In SHR, the heart content of ir-Dyn-A displayed a 6.5 fold increase at 8 weeks compared to age matched WKY. Older SHR showed a return of their heart ir-Dyn-A content to control (12 week-old) or below control values (16 week-old; 121 compared with 238 fmol/g tissue in WKY). Heart ir-Dyn-A in WKY and SHR eluted as a single peak on mu-Bondapak HPLC, corresponding with the retention time of synthetic Dyn-A. A local function for cardiac ir-Dyn-A is suggested by the presence in heart membrane preparations of a high affinity binding site for the kappa selective opioid ligand, [3H]U-69593, with KD of 6.4 (WKY) and 8.5 (SHR) nM and Bmax of 3.7 (WKY) and 3.6 (SHR) pmol/g protein. The alterations in the levels of cardiac ir-Dyn-A during the development of hypertension in SHR were analyzed in regard with the reported effects of Dyn-related peptides on heart natriuretic and sympathetic functions.
为了研究心脏强啡肽 A（Dyn - A）在遗传性高血压中的病理生理作用，我们检测了自发性高血压大鼠（SHR）心脏提取物中的免疫反应性（ir）- Dyn - A，并将其与年龄匹配的Wistar（WR）大鼠和Wistar Kyoto（WKY）大鼠进行比较。8周龄WK大鼠的心脏ir - Dyn - A含量（84 fmol/g组织）与年龄匹配的WKY大鼠（109 fmol/g组织）相比无显著差异。在对照WKY大鼠中，ir - Dyn - A水平除了在16周龄动物中与年轻动物相比显著升高（238 fmol/g组织）外，随年龄变化无显著差异（从109到117 fmol/g）。在SHR大鼠中，8周龄时心脏ir - Dyn - A含量相较于年龄匹配的WKY大鼠增加了6.5倍。年龄较大的SHR大鼠心脏ir - Dyn - A含量恢复到对照（12周龄）或低于对照值（16周龄；WKY大鼠为238 fmol/g组织，SHR大鼠为121 fmol/g组织）。WKY和SHR大鼠心脏中的ir - Dyn - A在μ - Bondapak高效液相色谱上洗脱为单峰，与合成Dyn - A的保留时间相对应。心脏膜制剂中存在对κ选择性阿片样配体[³H]U - 69593的高亲和力结合位点，其解离常数（KD）在WKY大鼠中为6.4 nM，在SHR大鼠中为8.5 nM，最大结合容量（Bmax）在WKY大鼠中为3.7 pmol/g蛋白质，在SHR大鼠中为3.6 pmol/g蛋白质，这提示心脏ir - Dyn - A具有局部功能。我们结合Dyn相关肽对心脏利钠和交感神经功能的报道效应，分析了SHR大鼠高血压发展过程中心脏ir - Dyn - A水平的变化。
