Longitudinal assessment of maternal-fetal Doppler parameters and maternal plasma level of matrix metalloproteinases 2 and 9.

OBJECTIVE: To assess the behavior as well as the comparison between maternal circulating level of biochemical markers (matrix metalloproteinases - MMP-9 and MMP-2) and maternal-fetal Doppler parameters in all three trimesters of pregnancy. METHODS: We performed a prospective longitudinal study with 33 healthy pregnant women in three periods of pregnancy: A1 (12w0-14w6d), A2 (22w0d-24w6d) and A3 (34w0d and 36w6d). The following maternal Doppler parameters were assessed: mean pulsatility index (PI) uterine artery, resistance index (RI) umbilical artery and RI middle cerebral artery. The maternal plasma concentrations of MMP-2 and MMP-9 were determined by enzyme immunoassay (ELISA). To compare two (A2 and A3) and three assessments (A1, A2 and A3), we used the paired Student t test and linear regression, respectively. To compare the biomechanical markers and maternal-fetal Doppler parameter, we used the Spearman correlation coefficient (ρ). RESULTS: We observed a significant decrease of PI uterine artery Doppler over the three trimesters of pregnancy (p < 0.01) and RI umbilical artery Doppler overt second to three trimester of pregnancy (p < 0.05). We did not observe significant difference in the maternal plasma level of MMP-2 and MMP-9 between the three trimesters. We did not also observe significant correlation between biochemical markers and maternal-fetal Doppler parameters. CONCLUSION: Maternal circulating level of MMPs did not modify throughout pregnancy and it did not show correlation with maternal-fetal Doppler parameters.

Assessment of nitrite oxide and maternal-fetal Doppler parameters during pregnancy.

OBJECTIVE: The objective was to evaluate and compare the whole blood nitrite concentration in the three trimesters of pregnancy. Additionally, we investigate whether there is any relation between nitrite concentrations and Doppler ultrasound analysis of some maternal and fetal vessels. METHODS: Thirty-three healthy pregnant women were examined at the first (11-14 weeks), second (20-24 weeks) and third trimester (34-36 weeks) of pregnancy. In the three exams, we determined the maternal whole blood nitrite concentration and uterine arteries Doppler analysis to determine pulsatility index (PI), and resistance index (RI). In the second and third trimester we also performed fetal umbilical and middle cerebral arteries PI and RI. We compared the concentrations of nitrite in three trimesters and correlated with Doppler parameters. RESULTS: No difference was observed in the whole blood nitrite concentrations across trimesters: 151.70 ± 77.90 nmol/ml, 142.10 ± 73.50 nmol/ml and 147.10 ± 87.30 nmol/ml; first, second and third trimesters, respectively. We found no difference in correlation between whole blood nitrite concentration and Doppler parameters from the evaluated vessels. CONCLUSIONS: In healthy pregnant women, the nitrite concentrations did not change across gestational trimesters and there was also no strong correlation with Doppler impedance indices from maternal uterine arteries and fetal umbilical and middle cerebral arteries.

[Role of nitric oxide in the control of the pulmonary circulation: physiological, pathophysiological, and therapeutic implications]. / Papel do óxido nítrico na regulação da circulação pulmonar: implicações fisiológicas, fisiopatológicas e terapêuticas.

Nitric oxide (NO) is an endogenous vasoactive compound that contributes to pulmonary vascular homeostasis and is produced by three nitric oxide synthase (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS (eNOS)-all three of which are present in the lung. Studies using pharmacological inhibitors or knockout mice have shown that eNOS-derived NO plays an important role in modulating pulmonary vascular tone and attenuating pulmonary hypertension. However, studies focusing on the role of iNOS have shown that this isoform contributes to the pathophysiology of acute lung injury and acute respiratory distress syndrome. This review aimed at outlining the role played by NO in the control of pulmonary circulation, both under physiological and pathophysiological conditions. In addition, we review the evidence that the L-arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological target in the treatment of pulmonary vascular diseases.

Papel do óxido nítrico na regulação da circulação pulmonar: implicações fisiológicas, fisiopatológicas e terapêuticas / Role of nitric oxide in the control of the pulmonary circulation: physiological, pathophysiological, and therapeutic implications

O nitric oxide (NO, óxido nítrico) é um mediador endógeno vasoativo que contribui para a homeostase vascular pulmonar. O NO é produzido por três isoformas das nitric oxide synthases (NOS, óxido nítrico sintases)-NOS neuronial (nNOS); NOS induzida (iNOS); e NOS endotelial (eNOS)-estando as três presentes no pulmão. Estudos que utilizaram inibidores farmacológicos ou camundongos knockout têm demonstrado que o NO derivado da eNOS desempenha importantes papéis ao modular o tônus vascular pulmonar e atenuar a hipertensão pulmonar. Por outro lado, estudos focados no papel da iNOS têm mostrado que essa isoforma contribui para a fisiopatologia da lesão pulmonar aguda e da síndrome do desconforto respiratório agudo. Esta revisão objetivou delinear o papel desempenhado pelo NO no controle da circulação pulmonar, tanto em condições fisiológicas como fisiopatológicas. Além disso, revisamos as evidências de que a via L-arginina-NO-guanosina monofosfato cíclico seja um importante alvo farmacológico para a terapia de doenças vasculares pulmonares.

Nitric oxide (NO) is an endogenous vasoactive compound that contributes to pulmonary vascular homeostasis and is produced by three nitric oxide synthase (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS (eNOS)-all three of which are present in the lung. Studies using pharmacological inhibitors or knockout mice have shown that eNOS-derived NO plays an important role in modulating pulmonary vascular tone and attenuating pulmonary hypertension. However, studies focusing on the role of iNOS have shown that this isoform contributes to the pathophysiology of acute lung injury and acute respiratory distress syndrome. This review aimed at outlining the role played by NO in the control of pulmonary circulation, both under physiological and pathophysiological conditions. In addition, we review the evidence that the L-arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological target in the treatment of pulmonary vascular diseases.