Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619: possible mechanism.
Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619: possible mechanism.
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妊娠期对 TxA2 模拟物 U-46619 的肺血管收缩作用的抵抗：可能的机制。
DOI：
10.1152/ajpregu.1997.272.6.r1734
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Venuto,R
中科院分区：
文献类型：
--
作者：
Losonczy,G;Brown,G;Mucha,I;Klocke,R;Muller,V;Merkely,B;Tornoci,L;Rosivall,L;Venuto,R
妊娠与血管对血管收缩剂化合物的敏感性降低有关。我们研究了家兔妊娠是否会引起肺血管系统对U-46619的低敏感性。对麻醉、机械通气的非妊娠（NP; n = 7）和晚期妊娠（P; n = 7）家兔进行了研究。静脉注射0.03、0.1和0.3 μ g/kg U-46619导致NP家兔的平均肺动脉压（MPAP）从基线值15 +/- 1至22 +/- 1 mgHg呈剂量依赖性升高。P兔静脉注射U-46619无明显MPAP反应。P组离体肺、通气肺和缓冲液灌注肺的肺动脉压反应也明显减弱（P < 0.001 vs. NP）。[125 I]BOP（另一种血栓烷（Tx）A2类似物）的肺动脉膜结合在P兔中为48 +/- 16 fmol受体/mg蛋白，在NP样品中为193 +/- 48 fmol受体/mg蛋白（P < 0.025）。P兔组织中受体亲和力[1/解离常数（KD）]也较低（P < 0.01 vs. NP）。P组尿中稳定的TxA 2代谢产物11-dehydro-TxB 2的排泄量明显低于NP组（P < 0.02），提示血管TxA 2受体的变化不可能由同源性脱敏引起。这些结果表明，在妊娠晚期，兔肺血管对U-46619的敏感性降低，同时，作为一个可能的后果，下调特定的受体。
Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late-pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 microgram/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 +/- 1 to 22 +/- 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P < 0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 +/- 16 fmol receptors/mg protein in P rabbits and 193 +/- 48 fmol receptors/mg protein in NP samples (P < 0.025). Receptor affinity [1/dissociation constant (KD)] was also lower in the tissue of P rabbits (P < 0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P < 0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.