Barron L A, Giardina J B, Granger J P, Khalil R A
Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MI, USA.
Hypertension. 2001 Sep;38(3 Pt 2):730-5. doi: 10.1161/01.hyp.38.3.730.
High-salt (HS) diet is often associated with increased vascular resistance and arterial pressure; however, the effects of HS intake on the vascular control mechanisms of arterial pressure during pregnancy are unclear. We investigated whether a HS diet during pregnancy is associated with increases in vascular reactivity. Active stress was measured in aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either normal-sodium (NS, 1%) or HS diet (8%) for 7 days. In endothelium-intact strips, phenylephrine (Phe) caused a concentration-dependent contraction that was greater in RUPP rats than in normal pregnant or virgin rats and was significantly enhanced in pregnant/HS and RUPP/HS rats compared with pregnant/NS and RUPP/NS rats, respectively. Removal of the endothelium enhanced the Phe-induced stress slightly in virgin rats and significantly in pregnant/NS but not in pregnant/HS, RUPP/NS, or RUPP/HS. In endothelium-intact strips, acetylcholine (ACh) caused a concentration-dependent relaxation that was reduced in RUPP/NS (max, 31%) compared with pregnant/NS rats (max, 75%). ACh relaxation was further reduced in pregnant/HS rats compared with pregnant/NS rats and in RUPP/HS rats compared with RUPP/NS rats. Pretreatment of endothelium-intact strips with N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L), to inhibit NO synthase, or with 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-6) mol/L), to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced contraction in pregnant/NS rats but not in pregnant/HS, RUPP/NS, or RUPP/HS rats. Basal and ACh-induced nitrite/nitrate production from aortic strips showed significant reduction in pregnant/HS rats compared with pregnant/NS rats but not in RUPP/HS rats compared with RUPP/NS rats. Sodium nitroprusside, an exogenous NO donor, caused relaxation of Phe contraction that was similar in virgin or pregnant rats on an NS or HS diet but was significantly reduced in RUPP/HS rats (ED(50) 6x10(-8) mol/L) compared with RUPP/NS rats (ED(50) 6x10(-9) mol/L). Thus, a HS diet in normal pregnant and RUPP rats is associated with increases in vascular reactivity. The enhanced vascular reactivity with the HS diet is possibly related to abnormalities in NO synthesis/release from the endothelium in normal pregnant rats and an additional decrease in the sensitivity of the smooth muscle to relaxation by NO in pregnant rats with reduced uterine perfusion pressure.
高盐（HS）饮食通常与血管阻力增加和动脉压升高有关；然而，孕期摄入高盐对动脉压血管控制机制的影响尚不清楚。我们研究了孕期高盐饮食是否与血管反应性增加有关。在未孕和正常怀孕的斯普拉格-道利大鼠以及通过降低子宫灌注压（RUPP）产生的高血压怀孕大鼠模型的主动脉条中测量主动应激，这些大鼠分别喂食正常钠（NS，1%）或高盐饮食（8%）7天。在内皮完整的条带中，去氧肾上腺素（Phe）引起浓度依赖性收缩，RUPP大鼠的收缩幅度大于正常怀孕或未孕大鼠，与怀孕/NS和RUPP/NS大鼠相比，怀孕/HS和RUPP/HS大鼠的收缩幅度分别显著增强。去除内皮后，Phe诱导的应激在未孕大鼠中略有增强，在怀孕/NS大鼠中显著增强，但在怀孕/HS、RUPP/NS或RUPP/HS大鼠中未增强。在内皮完整的条带中，乙酰胆碱（ACh）引起浓度依赖性舒张，与怀孕/NS大鼠（最大值为75%）相比，RUPP/NS大鼠（最大值为31%）的舒张幅度降低。与怀孕/NS大鼠相比，怀孕/HS大鼠的ACh舒张进一步降低，与RUPP/NS大鼠相比，RUPP/HS大鼠的ACh舒张也进一步降低。用N（G）-硝基-L-精氨酸甲酯（L-NAME，10（-4）mol/L）预处理内皮完整的条带以抑制一氧化氮合酶，或用1H-[1,2,4]恶二唑并[4,3]-喹喔啉-1-酮（ODQ，10（-6）mol/L）预处理以抑制平滑肌中的环鸟苷酸生成，可抑制怀孕/NS大鼠中ACh诱导的舒张并增强Phe诱导的收缩，但在怀孕/HS、RUPP/NS或RUPP/HS大鼠中无此作用。与怀孕/NS大鼠相比，怀孕/HS大鼠主动脉条的基础和ACh诱导的亚硝酸盐/硝酸盐生成显著减少，但与RUPP/NS大鼠相比，RUPP/HS大鼠无此现象。硝普钠是一种外源性一氧化氮供体，可使Phe收缩舒张，在喂食NS或HS饮食的未孕或怀孕大鼠中相似，但与RUPP/NS大鼠（ED（50）6x10（-9）mol/L）相比，RUPP/HS大鼠（ED（50）6x10（-8）mol/L）的舒张作用显著降低。因此，正常怀孕和RUPP大鼠的高盐饮食与血管反应性增加有关。高盐饮食导致的血管反应性增强可能与正常怀孕大鼠内皮一氧化氮合成/释放异常以及子宫灌注压降低的怀孕大鼠平滑肌对一氧化氮舒张的敏感性进一步降低有关。
