Masilamani S, Heesch C M
Department of Physiology, The Ohio State University, Columbus 43210-1218, USA.
Am J Physiol. 1997 Mar;272(3 Pt 2):R924-34. doi: 10.1152/ajpregu.1997.272.3.R924.
Previous experiments in anesthetized rats suggested that sympathoexcitatory responses were attenuated in pregnant (P) rats. The major progesterone metabolite, 3alpha-hydroxy-dihydroprogesterone (3alpha-OH-DHP), is elevated in pregnancy and reportedly potentiates central gamma-aminobutyric acidergic mechanisms, whereas the 3beta-isomer (3beta-OH-DHP) is inactive. This study obtained baroreflex curves in conscious rats by recording reflex changes in renal sympathetic nerve activity (RSNA) and heart rate (HR) due to perturbations in mean arterial pressure (MAP) [i.v. phenylephrine (PE) and nitroprusside (NTP)] in P rats and in virgin (V) rats before (control) and 15 min after infusion (i.v.) of 3alpha-OH-DHP or 3beta-OH-DHP. Baseline MAP was lower in P rats (P = 102 +/- 2 vs. V = 124 +/- 3 mmHg). Compared with V rats, P rats exhibited less "sympathetic reserve" to respond to a hypotensive challenge, as evidenced by decreased maximum NA and decreased slope of RSNA baroreflex responses to NTP. However, HR baroreflex curves were similar in P and V rats. Acute intravenous administration of 3alpha-OH-DHP to conscious V rats mimicked the effects of pregnancy. Baroreflex sympathoexcitatory responses were decreased, whereas baroreflex control of HR was unaffected. The 3beta-isomer of DHP had no effect on NA or HR baroreflex responses. These results suggest that pregnancy may have differential effects on baroreflex control of sympathetic outflow and HR, and the major metabolite of progesterone, 3alpha-OH-DHP, may contribute to this adaptation of pregnancy.
先前在麻醉大鼠身上进行的实验表明，妊娠（P）大鼠的交感神经兴奋反应有所减弱。主要的孕酮代谢产物3α-羟基二氢孕酮（3α-OH-DHP）在孕期会升高，据报道它能增强中枢γ-氨基丁酸能机制，而3β-异构体（3β-OH-DHP）则无活性。本研究通过记录清醒大鼠因平均动脉压（MAP）[静脉注射去氧肾上腺素（PE）和硝普钠（NTP）]扰动引起的肾交感神经活动（RSNA）和心率（HR）的反射变化，获得压力感受性反射曲线，实验对象为妊娠大鼠和未孕（V）大鼠，分别在输注（静脉注射）3α-OH-DHP或3β-OH-DHP之前（对照）和之后15分钟进行。妊娠大鼠的基线MAP较低（P = 102±2 vs. V = 124±3 mmHg）。与未孕大鼠相比，妊娠大鼠对低血压刺激的“交感神经储备”反应较小，这表现为对NTP的最大去甲肾上腺素（NA）反应降低以及RSNA压力感受性反射反应斜率降低。然而，妊娠大鼠和未孕大鼠的HR压力感受性反射曲线相似。对清醒的未孕大鼠急性静脉注射3α-OH-DHP可模拟妊娠的效应。压力感受性反射交感神经兴奋反应降低，而对HR的压力感受性反射控制不受影响。DHP的3β-异构体对NA或HR压力感受性反射反应无影响。这些结果表明，妊娠可能对交感神经输出和HR的压力感受性反射控制有不同影响，孕酮的主要代谢产物3α-OH-DHP可能有助于妊娠的这种适应性变化。
