雌性生长受限后代对急性 ANG II 的超敏反应通过卵巢切除术而加剧。
Hypersensitivity to acute ANG II in female growth-restricted offspring is exacerbated by ovariectomy.
机构信息
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
出版信息
Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R1199-205. doi: 10.1152/ajpregu.00219.2011. Epub 2011 Aug 10.
Female growth-restricted offspring are normotensive in adulthood. However, ovariectomy induces a marked increase in mean arterial pressure (MAP) that is abolished by renin angiotensin system (RAS) blockade, suggesting RAS involvement in the etiology of hypertension induced by ovariectomy in adult female growth-restricted offspring. Blockade of the RAS also abolishes hypertension in adult male growth-restricted offspring. Moreover, sensitivity to acute ANG II is enhanced in male growth-restricted offspring. Thus, we hypothesized that an enhanced sensitivity to acute ANG II may contribute to hypertension induced by ovariectomy in female growth-restricted offspring. Female offspring were subjected to ovariectomy (OVX) or sham ovariectomy (intact) at 10 wk of age. Cardio-renal hemodynamic parameters were determined before and after an acute infusion of ANG II (100 ng·kg(-1)·min(-1) for 30 min) at 16 wk of age in female offspring pretreated with enalapril (40 mg·kg(-1)·day(-1) for 7 days). Acute ANG II induced a significant increase in MAP in intact growth-restricted offspring (155 ± 2 mmHg, P < 0.05) relative to intact control (145 ± 4 mmHg). Ovariectomy augmented the pressor response to ANG II in growth-restricted offspring (163 ± 2 mmHg, P < 0.05), with no effect in control (142 ± 2 mmHg). Acute pressor responses to phenylephrine did not differ in growth-restricted offspring relative to control, intact, or ovariectomized. Furthermore, renal hemodynamic responses to acute ANG II were significantly enhanced only in ovariectomized female growth-restricted offspring. Thus, these data suggest that enhanced responsiveness to acute ANG II is programmed by intrauterine growth restriction and that sensitivity to acute ANG II is modulated by ovarian hormones in female growth-restricted offspring.
女性生长受限后代在成年时血压正常。然而，卵巢切除术会导致平均动脉压（MAP）显著升高，而肾素-血管紧张素系统（RAS）阻断可消除这种升高，表明 RAS 参与了成年女性生长受限后代卵巢切除术后高血压的发生。RAS 阻断也可消除成年雄性生长受限后代的高血压。此外，雄性生长受限后代对急性 ANG II 的敏感性增强。因此，我们假设对急性 ANG II 的敏感性增强可能导致雌性生长受限后代卵巢切除术后的高血压。雌性后代在 10 周龄时接受卵巢切除术（OVX）或假卵巢切除术（完整）。在 16 周龄时，雌性后代在预处理恩那普利（40mg·kg(-1)·天(-1)，7 天）后，急性输注 ANG II（100ng·kg(-1)·min(-1)，30 分钟）前后测定心肺肾血流动力学参数。急性 ANG II 引起完整生长受限后代 MAP 显著升高（155±2mmHg，P<0.05），与完整对照组（145±4mmHg）相比。卵巢切除术增强了生长受限后代对 ANG II 的升压反应（163±2mmHg，P<0.05），对对照组（142±2mmHg）无影响。生长受限后代的急性去甲肾上腺素升压反应与对照组、完整或卵巢切除的无差异。此外，急性 ANG II 仅在卵巢切除的雌性生长受限后代中显著增强了肾血流动力学反应。因此，这些数据表明，对急性 ANG II 的反应增强是由宫内生长受限编程的，而对急性 ANG II 的敏感性是由雌性生长受限后代的卵巢激素调节的。
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