Payne Jason A, Alexander Barbara T, Khalil Raouf A
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Miss, USA.
Hypertension. 2003 Oct;42(4):768-74. doi: 10.1161/01.HYP.0000084990.88147.0C. Epub 2003 Jul 21.
Low birth weight as the result of placental insufficiency increases the risk of hypertension in young adults; however, the vascular mechanisms involved are unclear. We tested the hypothesis that intrauterine fetal growth restriction caused by placental insufficiency results in low-birth-weight offspring with impaired endothelium-dependent vascular relaxation, enhanced vasoconstriction, and hypertension. The body weight and arterial pressure were measured in young (4 weeks), adolescent (8 weeks), and adult (12 weeks) male offspring of normal pregnant rats and pregnant rats with reduced uteroplacental perfusion (intrauterine growth-restricted, IUGR), and aortic strips were isolated for measurement of isometric contraction. The body weight was lower whereas the arterial pressure was higher in IUGR than normal rats at 4 weeks (113+/-3 versus 98+/-2), 8 weeks (133+/-3 versus 121+/-6), and 12 weeks (144+/-4 versus 131+/-3 mm Hg). Phe (10(-5) mol/L) caused an increase in active stress that was greater in IUGR than in normal rats at 4 weeks (12.4 versus 7.8), 8 weeks (13.3 versus 8.4), and 12 weeks (14.6 versus 9.0x10(4) N/m2). Removal of the endothelium enhanced Phe-induced stress in normal but not IUGR rats. In endothelium-intact strips, acetylcholine (ACh) caused relaxation of Phe contraction and induced nitrite/nitrate production that were smaller in IUGR than normal rats. L-NAME (10(-4) mol/L), which inhibits NO synthase, or ODQ (10(-5) mol/L), which inhibits cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe contraction in normal but not IUGR rats. Thus endothelium-dependent NO-mediated vascular relaxation is inhibited in IUGR offspring of pregnant rats with reduced uteroplacental perfusion, and this may explain the increased vascular constriction and arterial pressure in young adults with low birth weight.
胎盘功能不全导致的低出生体重会增加年轻人患高血压的风险；然而，其中涉及的血管机制尚不清楚。我们验证了这样一个假设，即胎盘功能不全引起的子宫内胎儿生长受限会导致出生体重低的后代出现内皮依赖性血管舒张受损、血管收缩增强和高血压。对正常妊娠大鼠和子宫胎盘灌注减少的妊娠大鼠（子宫内生长受限，IUGR）的雄性幼崽（4周龄）、青春期大鼠（8周龄）和成年大鼠（12周龄）测量体重和动脉血压，并分离主动脉条进行等长收缩测量。在4周龄（113±3对98±2）、8周龄（133±3对121±6）和12周龄（144±4对131±3 mmHg）时，IUGR大鼠的体重低于正常大鼠，而动脉血压高于正常大鼠。苯肾上腺素（10⁻⁵ mol/L）引起的主动张力增加在4周龄（12.4对7.8）、8周龄（13.3对8.4）和12周龄（14.6对9.0×10⁴ N/m²）时IUGR大鼠比正常大鼠更大。去除内皮可增强正常大鼠而非IUGR大鼠中苯肾上腺素诱导的张力。在内皮完整的血管条中，乙酰胆碱（ACh）引起苯肾上腺素收缩的舒张并诱导亚硝酸盐/硝酸盐生成，IUGR大鼠中的这些反应比正常大鼠小。抑制一氧化氮合酶的L-精氨酸甲酯（10⁻⁴ mol/L）或抑制平滑肌中cGMP生成的ODQ（10⁻⁵ mol/L），抑制正常大鼠而非IUGR大鼠中ACh诱导的舒张并增强苯肾上腺素收缩。因此，子宫胎盘灌注减少的妊娠大鼠的IUGR后代中内皮依赖性一氧化氮介导的血管舒张受到抑制，这可能解释了低出生体重的年轻人中血管收缩增加和动脉血压升高的原因。
