Okogbule-Wonodi A C, Ibe B O, Yue B W, Hsu S, Raj J U
UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, California, 90509, USA.
Mol Genet Metab. 1998 Nov;65(3):229-37. doi: 10.1006/mgme.1998.2756.
The transition from fetal to newborn life is marked by a reduction in pulmonary vascular tone mediated by the intracellular second messengers, cGMP and cAMP. We have compared the rates of phosphodiesterase (PDE)-catalyzed hydrolysis of cGMP and cAMP in intrapulmonary vessels of fetal (146 +/- 2 days gestation) and newborn (3-7-day-old) lambs, each n = 6. Lung vessels of second to sixth generations were dissected and cytosol was prepared by differential centrifugation. PDE activity in cytosol was determined by radiometric assay of the hydrolysis of exogenous nucleotides at 30 degrees C for 10 min. Rates of hydrolysis (pmol/min/mg protein) of cGMP were 225 +/- 38 in fetal arteries and different from 151 +/- 7 in veins. In newborn vessels, the rates were 155 +/- 49 and 63 +/- 13 in arteries and veins, respectively. Rates of cAMP hydrolysis by the fetus were 80 +/- 11 in arteries and 45 +/- 16 veins. In newborn lambs the rates were 69 +/- 10 in arteries and different from 18 +/- 4 in veins. Inhibition of PDE activity by zaprinast, a cGMP-specific PDE inhibitor, and rolipram, a cAMP-specific PDE inhibitor, was more in veins of fetal and newborn lambs. Our data show that rates of hydrolysis of the cyclic nucleotides were faster in fetal vessels than in the newborn. We speculate that this would result in a greater accumulation of the cyclic nucleotides in newborn vessels, particularly the veins, and therefore endow the veins with less vascular tone.
从胎儿期到新生儿期的转变以细胞内第二信使环磷酸鸟苷（cGMP）和环磷酸腺苷（cAMP）介导的肺血管张力降低为标志。我们比较了胎儿（妊娠146±2天）和新生（3 - 7日龄）羔羊肺内血管中磷酸二酯酶（PDE）催化的cGMP和cAMP水解速率，每组n = 6。解剖第二代至第六代肺血管，通过差速离心制备胞质溶胶。通过在30℃下对外源核苷酸水解进行放射性测定，确定胞质溶胶中的PDE活性，持续10分钟。胎儿动脉中cGMP的水解速率（pmol/分钟/毫克蛋白）为225±38，与静脉中的151±7不同。在新生血管中，动脉和静脉中的速率分别为155±49和63±13。胎儿动脉中cAMP的水解速率为80±11，静脉中为45±16。在新生羔羊中，动脉中的速率为69±10，与静脉中的18±4不同。cGMP特异性PDE抑制剂扎普司特和cAMP特异性PDE抑制剂咯利普兰对胎儿和新生羔羊静脉中PDE活性的抑制作用更强。我们的数据表明，胎儿血管中环核苷酸的水解速率比新生血管中的更快。我们推测，这将导致新生血管，尤其是静脉中，环核苷酸的积累更多，从而使静脉具有更低的血管张力。
