Gangula P R, Wimalawansa S J, Yallampalli C
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
Am J Obstet Gynecol. 1997 Apr;176(4):894-900. doi: 10.1016/s0002-9378(97)70618-5.
We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent.
Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily.
Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment period, and these effects were lost when progesterone treatment was stopped. Again, at these doses calcitonin gene-related peptide and progesterone were each ineffective alone.
Calcitonin gene-related peptide reverses the N(G)-nitro-L-arginine methyl ester-induced hypertension during pregnancy, when progesterone levels are elevated, but not post partum or in ovariectomized nonpregnant rats. The blood pressure-lowering effects of calcitonin gene-related peptide were restored in both postpartum and ovariectomized rats with progesterone treatment. Therefore we conclude that progesterone modulates vasodilator effects of calcitonin gene-related peptide in hypertensive rats.
我们最近报道，降钙素基因相关肽可逆转妊娠大鼠中由N（G）-硝基-L-精氨酸甲酯诱导产生的高血压。在本研究中，我们调查了降钙素基因相关肽的这些血管舒张作用是否依赖于孕酮。
从妊娠第17天至产后第8天，通过渗透微型泵单独或联合向每组五只妊娠大鼠输注降钙素基因相关肽或N（G）-硝基-L-精氨酸甲酯，或向未妊娠的去卵巢大鼠输注8天。在产后第1至6天以及去卵巢后6天注射孕酮。每天测量收缩压。
接受N（G）-硝基-L-精氨酸甲酯的动物在妊娠和产后期间血压显著升高。向这些大鼠联合给予降钙素基因相关肽可逆转妊娠期间的高血压，但产后期间无效。在本研究中使用的剂量下，单独给予降钙素基因相关肽对血压无显著影响。然而，它降低了这些动物中与N（G）-硝基-L-精氨酸甲酯相关的胎儿死亡率和生长受限。降钙素基因相关肽仅在孕酮治疗期间逆转了N（G）-硝基-L-精氨酸甲酯输注的产后大鼠的高血压，当停止孕酮治疗时这些作用消失。单独的孕酮或降钙素基因相关肽均无效。为了进一步证实这些观察结果，在去卵巢成年大鼠中测试了孕酮的作用。与产后大鼠的结果相似，降钙素基因相关肽完全逆转了接受孕酮注射的N（G）-硝基-L-精氨酸甲酯处理大鼠的血压升高。降钙素基因相关肽的作用仅在孕酮治疗期间明显，当停止孕酮治疗时这些作用消失。同样，在这些剂量下，降钙素基因相关肽和孕酮单独使用均无效。
降钙素基因相关肽在孕酮水平升高的妊娠期间可逆转N（G）-硝基-L-精氨酸甲酯诱导的高血压，但在产后或未妊娠的去卵巢大鼠中则不然。通过孕酮治疗，降钙素基因相关肽的降压作用在产后大鼠和去卵巢大鼠中均得以恢复。因此我们得出结论，孕酮调节降钙素基因相关肽在高血压大鼠中的血管舒张作用。
