Gangula P R, Supowit S C, Wimalawansa S J, Zhao H, Hallman D M, DiPette D J, Yallampalli C
Department of Obstetrics and Gynecology, University of Texas Medical Branch (Galveston), USA.
Hypertension. 1997 Jan;29(1 Pt 2):248-53. doi: 10.1161/01.hyp.29.1.248.
Inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. We previously reported that administration of calcitonin gene-related peptide (CGRP) reduces the blood pressure and fetal death produced by L-NAME. To determine the hemodynamic role of endogenous CGRP in this setting, CGRP8-37, a CGRP receptor antagonist, was used. In addition, CGRP mRNA and peptide levels were determined in dorsal root ganglia. L-NAME or control rats had intravenous (for drug administration) and arterial (for continuous mean blood pressure monitoring) catheters surgically placed and were studied in the conscious unrestrained state. Baseline blood pressure was higher in the L-NAME than the control rats on days 19, 20, and 21 or pregnancy and postpartum day 1. Vehicle administration did not change blood pressure in any group, and CGRP8-37 (100 micrograms) did not change blood pressure in control groups. However, CGRP8-37 administration to the L-NAME rats further increased blood pressure (P < .05) on days 19 (8 +/- 1), 20 (12 +/- 2), and 21 (7 +/- 1) of gestation but was without effect on postpartum day 1. Furthermore, CGRP mRNA or peptide levels in dorsal root ganglia were not different between the L-NAME and control rats at any of the time points studied. These data indicate that in experimental preeclampsia, CGRP is playing a compensatory vasodilator role to attenuate the elevated blood pressure. The mechanism of this effect appears to be an enhanced vascular responsiveness to CGRP that is attenuated after the birth of pups.
用NG-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮生成会增加妊娠大鼠的血压和胎儿死亡率。我们之前报道过，给予降钙素基因相关肽（CGRP）可降低L-NAME所致的血压升高和胎儿死亡。为了确定内源性CGRP在此情况下的血流动力学作用，使用了CGRP受体拮抗剂CGRP8-37。此外，还测定了背根神经节中CGRP mRNA和肽水平。L-NAME组或对照组大鼠通过手术植入静脉导管（用于给药）和动脉导管（用于连续监测平均血压），并在清醒无拘束状态下进行研究。在妊娠第19、20和21天以及产后第1天，L-NAME组大鼠的基线血压高于对照组。给予溶剂在任何组中均未改变血压，给予CGRP8-37（100微克）在对照组中也未改变血压。然而，在妊娠第19天（8±1）、20天（12±2）和21天（7±1）给予L-NAME组大鼠CGRP8-37会进一步升高血压（P<0.05），但在产后第1天无此作用。此外，在所研究的任何时间点，L-NAME组和对照组大鼠背根神经节中的CGRP mRNA或肽水平均无差异。这些数据表明，在实验性先兆子痫中，CGRP发挥着代偿性血管舒张作用以减轻血压升高。这种作用机制似乎是血管对CGRP的反应性增强，而在幼崽出生后这种反应性会减弱。
