[Effect of pravastatin on tetrahydrobiopterin-sensitive and -resistant NO synthase activity of preeclamptic placentas].

The treatment of preeclampsia, which occurs in 3-8% of pregnancies, is not yet resolved. In preeclampsia, NO synthesis is insufficient, which can contribute to hypertension, proteinuria and abnormal vascularization of the placenta. Decreased NO synthesis in the preeclamptic placenta may also be due to a decrease in the affinity of NO synthase for tetrahydrobiopterin (BH4), resulting in BH4 resistance. In recent years, pravastatin has been shown to prevent preeclampsia in animal models and in human studies. One of the known pleiotropic effects of pravastatin is that it increases NO synthase activity. Description of the effect of pravastatin on BH4-resistant NO synthase activity in the preeclamptic placenta. NO synthase activity in the placental microsome was measured with C14 arginine substrate using healthy (n = 9) and preeclamptic (n = 9) samples. NO synthase activity was measured at 0.02 µM, physiological at 0.20 µM and pharmacological at 50 µM BH4. One of the 9 preeclamptic patients was BH4-resistant; physiologic BH4 concentration did not significantly increase NO synthase activity, whereas healthy placental microsomes showed a mean increase of 60% (p<0.01), and BH4-sensitive preeclamptic specimen showed a 67% (p<0.01) increase. 10 µM pravastatin increased NO synthase activity by 32-38% at each BH4 concentration in healthy, BH4-sensitive and BH4-resistant preeclampsia samples. 10 µM pravastatin increased BH4-resistant placental NO synthase activity to a similar extent as placental physiological BH4 concentration (0.06-0.20 µM) to BH4-sensitive NO synthase activity. The NO synthase activity of BH4-resistant preeclamptic placenta can be increased by pravastatin to physiological level. Orv Hetil. 2020; 161(10): 389-395.