Daubert Daisy L, Chung Mee-Young, Brooks Virginia L
Oregon Health & Science University, Department of Physiology and Pharmacology, Portland, Oregon 97239, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Jun;292(6):R2188-95. doi: 10.1152/ajpregu.00614.2006. Epub 2007 Feb 15.
Pregnancy decreases baroreflex gain, but the underlying mechanism is unclear. Insulin resistance, which has been associated with reduced transport of insulin into the brain, is a consistent feature of many conditions exhibiting impaired baroreflex gain, including pregnancy. Therefore, using conscious pregnant and nonpregnant rabbits, we tested the novel hypothesis that the pregnancy-induced impairment in baroreflex gain is due to insulin resistance and reduced brain insulin. Baroreflex gain was determined by quantifying changes in heart rate in response to stepwise steady-state changes in arterial pressure, secondary to infusion of nitroprusside and phenylephrine. We found that insulin sensitivity and baroreflex gain were strongly correlated in nonpregnant and term pregnant rabbits (r2 = 0.59). The decrease in insulin sensitivity and in baroreflex gain exhibited similar time courses throughout pregnancy, reaching significantly lower levels at 3 wk of gestation and remaining reduced at 4 wk (term is 31 days). Treatment of rabbits with the insulin-sensitizing drug rosiglitazone during pregnancy almost completely normalized baroreflex gain. Finally, pregnancy significantly lowered cerebrospinal fluid insulin concentrations. These data identify insulin resistance as a mechanism underlying pregnancy-induced baroreflex impairment and suggest, for the first time in any condition, that decreased brain insulin concentrations may be the link between reductions in peripheral insulin sensitivity and baroreflex gain.
怀孕会降低压力感受性反射增益，但其潜在机制尚不清楚。胰岛素抵抗与胰岛素向脑内转运减少有关，是许多压力感受性反射增益受损的情况（包括怀孕）的一个共同特征。因此，我们使用清醒的怀孕和未怀孕兔子，检验了一个新的假说，即怀孕引起的压力感受性反射增益受损是由于胰岛素抵抗和脑胰岛素减少。通过量化静脉注射硝普钠和去氧肾上腺素后，因动脉压逐步稳态变化而引起的心率变化来确定压力感受性反射增益。我们发现，在未怀孕和足月怀孕的兔子中，胰岛素敏感性与压力感受性反射增益密切相关（r2 = 0.59）。在整个孕期，胰岛素敏感性和压力感受性反射增益的降低呈现出相似的时间进程，在妊娠3周时显著降低，并在4周时（足月为31天）仍保持在较低水平。在怀孕期间用胰岛素增敏药物罗格列酮治疗兔子，几乎可使压力感受性反射增益完全恢复正常。最后，怀孕显著降低了脑脊液胰岛素浓度。这些数据确定胰岛素抵抗是怀孕引起的压力感受性反射受损的一种机制，并首次在任何情况下表明，脑胰岛素浓度降低可能是外周胰岛素敏感性降低与压力感受性反射增益降低之间的联系。
