Donatori di nitrossido nell'ipertensione gestazionale e nella riduzione della crescita intrauterina

Nitric oxide (NO) certainly holds the main role in the paracrine regulation of vascular tone. It has been shown that the administration of inhibitor of NO synthesis (L-NAME) in rat increases mean blood pressure. Furthermore, the continuous L-NAME infusion produces a like-eclamptic syndrome. The infusion of L-arginine in humans produces a decrease of systolic and diastolic blood pressure, above all in hypertensive subjects. But pregnant women affected by eclampsia show a decreased activity of L- arginine/NO system. The patients with eclampsia could present an inhibition of release and/or inactivation of NO. Recently, we evaluated the use of glyceriltrinitrate (GTN) administered sublingually by spray (2 pufs: 800 μg of GTN, Natispray®, Teofarma) in ten pregnant women affected by pregnancy induced hypertension with or without IUGR and ten controls (healthy pregnant women). We observed after 5 minutes from drug administration some significant statistically variations, such as an increase of maternal heart rate, a decrease of maternal diastolic blood pressure and a decrease of impedance flow indexes either in the placement-uterine artery (reduction of RI) either in the umbilical artery (reduction of PI). At 10 minutes from the administration we observed a decrease of maternal systolic blood pressure whereas impedance flow indexes of placental-uterine artery and umbilical artery were not statistically significantly changed. At 20 minutes after the administration all these parameters returned to basal balues. We think that may be important the use of an acute test with NO-donors (NO test) in order to distinguish between cases of IUGR due to partial and/or failed hemodynamic changes and cases not influenced by hemodynamic characteristics. Similar effects have been demonstrated also in patients treated with L-arginine. Three groups of nine pregnant women have been infused with 30 g. i.v. of L- arginine for 30 minutes. The control group was composed of healthy pregnant women, whereas the others two groups included patients with intrauterine growth retardation, one without (IUGR-1) and the other with (IUGR-2) increase of utero-placental resistance indexes. In the IUGR-2 group, the infusion of L-arginine showed a significant decrease of resistance index in the uterine artery (not placental), there was a decrease in P1 basal values of 14%. No hemodynamic changes were observed in the control group and in the IUGR-1 group. During infusion of L-arginine a significant increase of hematic levels of nitrites was noticed, whereas blood pressure remained unchanged. Conclusions: It was hypothesized that NO release is the main mechanism of the uterine quiescence during pregnancy, so that NO-donors could be a new therapeutic approach in cases of preterm labor. Furthermore, our data seem to indicate that in cases of IUGR and/or eclampsia there is an alteration of L- arginine-NO system, and that the administration of either L-arginine and NO- donor drugs might improve the utero-placental circulation. The NO test allows to distinguish between pathological conditions that can benefit by this treatment and pathological conditions that couldn't obtain any advantage but sometimes dangerous side effects. However it is necessary to evaluate the effects of chronic administration of these drugs, considering the possible tolerance and the known side effects.