Differences between macrovascular and microvascular functions in pregnant women with chronic hypertension or preeclampsia: new insights into maternal vascular health.

Introduction: Hypertensive disorders of pregnancy, including chronic hypertension (CH) and preeclampsia (PE), stand as prominent global contributors to maternal and perinatal morbidity and mortality. Endothelial dysfunction plays a central role in the pathophysiology of these conditions. This dysfunction impacts blood flow and the regulation of vascular response, potentially leading to alterations in the remodeling of blood vessels.

Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia.

Preeclampsia (PE) is a hypertensive disorder of pregnancy and is associated with increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) levels. Placental ischemia and hypoxia are hypothesized as initial pathophysiological events of PE. Nitrite (NO metabolite) may be recycled back to NO in ischemic and hypoxic tissues.

Maternal pregnancy hypertension impairs nitric oxide formation and results in increased arterial blood pressure in first-generation offspring female rats.

Objectives: Maternal endothelial dysfunction in pregnancy hypertension is related to impairment of nitric oxide (NO) formation. However, NO levels and hemodynamic repercussions on the female offspring remain unclear. Therefore, this study hypothesized that maternal pregnancy hypertension reduces circulating NO metabolites and increases arterial blood pressure in first-generation offspring female rats.

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth.

Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats.

Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (HS), as an alternative for counteracting vascular dysfunction, is incompletely clear in hypertensive disorders of pregnancy. Therefore, PVAT-derived HS-induced vasodilation was investigated in pregnancy hypertension-induced endothelial dysfunction.

Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide.

Aims: Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension.

Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats.

Preeclampsia is a maternal hypertension disorder associated with vascular dysfunction and fetal and placental growth restrictions. Placental ischemia is suggested as the primary trigger of preeclampsia-associated impairments of both endothelium-derived nitric oxide (NO) and the vascular activity of extracellular matrix metalloproteinase-2 (MMP-2). Reduced uteroplacental perfusion pressure (RUPP) is a placental ischemia model of preeclampsia.

Sildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertension.

Lead (Pb) reduces NO bioavailability, impairs the antioxidant system, and increases the generation of reactive oxygen species (ROS). Pb-induced oxidative stress may be responsible for the associated endothelial dysfunction. Sildenafil has shown nitric oxide (NO)-independent action, including antioxidant effects.

Pravastatin Prevents Increases in Activity of Metalloproteinase-2 and Oxidative Stress, and Enhances Endothelium-Derived Nitric Oxide-Dependent Vasodilation in Gestational Hypertension.

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy and has been associated with placental growth restriction. The pre-eclamptic placenta releases free radicals to maternal circulation, thus increasing oxidative stress. An impaired redox state leads to reduction in circulating nitric oxide (NO) levels and activation of extracellular matrix metalloproteinases (MMPs).

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group).

Circulating levels of hydrogen sulphide negatively correlate to nitrite levels in gestational hypertensive and preeclamptic pregnant women.

Endothelial dysfunction is a hallmark of preeclampsia and the role of nitric oxide (NO) has been extensively studied in this pregnancy complication. In recent years, hydrogen sulphide (H S) has arisen as a new gasotransmitter with an impact on endothelial function. However, the involvement of H S in the pathophysiology of preeclampsia is not fully understood, and only a few studies with limited sample size have investigated circulating levels of H S in preeclamptic patients.

Anticontractile Effect of Perivascular Adipose Tissue But Not of Endothelium Is Enhanced by Hydrogen Sulfide Stimulation in Hypertensive Pregnant Rat Aortae.

Perivascular adipose tissue (PVAT) modulates the vascular tone. Hydrogen sulfide (H2S) is synthetized by cystathionine gamma-lyase (CSE) in brown PVAT. Modulation of vascular contractility by H2S is, in part, adenosine triphosphate (ATP)-sensitive potassium channels dependent.

Reductions of Circulating Nitric Oxide are Followed by Hypertension during Pregnancy and Increased Activity of Matrix Metalloproteinases-2 and -9 in Rats.

Hypertensive pregnancy has been associated with reduced nitric oxide (NO), bioavailability, and increased activity of matrix metalloproteinases (MMPs). However, it is unclear if MMPs activation is regulated by NO during pregnancy. To this end, we examined activity of MMP-2 and MMP-9 in plasma, placenta, uterus and aorta, NO bioavailability, oxidative stress, systolic blood pressure (SBP), and fetal-placental development at the early, middle, and late pregnancy stages in normotensive and Nω-Nitro-L-arginine methyl-ester (L-NAME)-induced hypertensive pregnancy in rats.

Effects of fast versus slow-releasing hydrogen sulfide donors in hypertension in pregnancy and fetoplacental growth restriction.

Hydrogen sulfide (HS) is a vasorelaxant gas with therapeutic potential in several diseases. However, effects of HS donors in hypertensive pregnancy complicated by feto-placental growth restriction are unclear. Therefore, we aimed to examine and compare the effects of fast-releasing HS donor (sodium hydrosulfide-NaHS) and slow-releasing HS donor (GYY4137) in hypertension-in-pregnancy.

Hypertension, augmented activity of matrix metalloproteinases-2 and -9 and angiogenic imbalance in hypertensive pregnancy are attenuated by doxycycline.

Preeclampsia is manifested as maternal hypertension and fetal growth restriction. Matrix metalloproteinases (MMPs) are involved in hypertension and doxycycline reduces blood pressure by inhibition of MMPs. Moreover, excessive levels of MMPs and reduced nitric oxide (NO) bioavailability have been related to preeclampsia.

Placental nitric oxide formation and endothelium-dependent vasodilation underlie pravastatin effects against angiogenic imbalance, hypertension in pregnancy and intrauterine growth restriction.

Pre-eclampsia and hypertensive disorders of pregnancy are frequently associated with foeto-placental growth restriction, and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy.

Increases in placental nitric oxide, but not nitric oxide-mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy.

Dysregulation of hydrogen sulphide (H S) producing enzymes has been related to hypertensive pregnancy, and H S donor, sodium hydrosulphide (NaHS) exerts antihypertensive effects, modulates angiogenic factors production and acts as an antioxidant. Moreover, reduction in nitric oxide (NO) bioavailability is related to hypertensive pregnancy and H S may interact with NO, modulating its production. We aimed to investigate the NaHS effects in hypertension-in-pregnancy and also in feto-placental parameters.

Clinical and Experimental Evidences of Hydrogen Sulfide Involvement in Lead-Induced Hypertension.

Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (HS) have been reported previously. However, no studies examined involvement of HS in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished HS plasmatic levels.

Maternal hypertension and feto-placental growth restriction is reversed by sildenafil: Evidence of independent effects of circulating nitric oxide levels.

Sildenafil has shown nitric oxide (NO)-independent pleiotropic effects, however the mechanisms involved are unclear. We investigated the protective effects of sildenafil against hypertension in pregnancy and feto-placental growth restriction induced by NO inhibition, and if sodium nitrite-derived NO formation influences sildenafil effects. We evaluated the plasmatic levels of NO metabolites, cyclic guanosine monophosphate (cGMP), oxidative stress and myeloperoxidase, which are involved in endothelial dysfunction during hypertension in pregnancy.

Cardiac myeloperoxidase activity is elevated in hypertensive pregnant rats.

Myeloperoxidase (MPO) is released from activated neutrophils. The inflammation in preeclampsia was found to be associated with endothelial dysfunction. We hypothesized that cardiac and circulating MPO levels are elevated in hypertensive pregnancy.

Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy.

Preeclampsia is a form of hypertension-in-pregnancy (HTN-Preg) with unclear mechanism. Generalized reduction of uterine perfusion pressure (RUPP) could be an initiating event leading to uteroplacental ischemia, angiogenic imbalance, and HTN-Preg. Additional regional differences in uteroplacental blood flow could further affect the pregnancy outcome and increase the risk of preeclampsia in twin or multiple pregnancy, but the mechanisms involved are unclear.

Sodium hydrosulfide prevents hypertension and increases in vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 in hypertensive pregnant rats.

Sodium hydrosulfide (NaHS) has presented antihypertensive and antioxidant effects and may reduce circulating soluble fms-like tyrosine kinase-1 (sFlt-1). We examined whether NaHS prevents maternal and fetal detrimental changes in a model of hypertension in pregnancy induced by N(G)-nitro-L-arginine methyl ester (L-NAME). Forty pregnant rats were divided into four groups (n = 10 per group): Norm-Preg, Preg + NaHS, HTN-Preg, or HTN-Preg + NaHS.

Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor.

Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood.

Exposure to fipronil elevates systolic blood pressure and disturbs related biomarkers in plasma of rats.

Recent reports show that fipronil affects non-target organisms, including environmental species populations and potentially humans. We aimed to examine if fipronil exposure affects the systolic blood pressure and related biomarkers. Thus, fipronil was orally administered to rats (30 mg/kg/day) during 15 days (Fipronil group) or physiological solution (Control group).

Sodium Nitrite Prevents both Reductions in Circulating Nitric Oxide and Hypertension in 7-Day Lead-Treated Rats.

Hypotensive effects of oral sodium nitrite have been reported as alternative sources of nitric oxide (NO) formation in animals and human beings. Reductions in NO bioavailability were observed in lead-induced hypertension. However, no previous study has examined whether a single daily dose of sodium nitrite prevents the reductions in the NO bioavailability in lead-induced hypertension.