Cerebral sympatholysis: experiments on in vivo cerebrovascular regulation and ex vivo cerebral vasomotor control.

Whether cerebral sympathetic-mediated vasomotor control can be modulated by local brain activity remains unknown. This study tested the hypothesis that the application or removal of a cognitive task during a cold pressor test (CPT) would attenuate and restore decreases in cerebrovascular conductance (CVC), respectively. Middle cerebral artery blood velocity (transcranial Doppler) and mean arterial pressure (finger photoplethysmography) were examined in healthy adults ( = 16; 8 females and 8 males) who completed a control CPT, followed by a CPT coupled with a cognitive task administered either ) 30 s after the onset of the CPT and for the duration of the CPT or ) at the onset of the CPT and terminated 30 s before the end of the CPT (condition order was counterbalanced).

CP55940-induced vasorelaxation is endothelial-dependent and mediated by the CB1R through NOS, COX and EDHF pathways in porcine cerebral arteries.

Using swine as an experimental model, we examined whether the cannabinoid receptors (CB1R and CB2R) modulated vasomotor tone in isolated pial arteries. It was hypothesized that the CB1R would mediate cerebral artery vasorelaxation in an endothelial-dependent manner. First-order pial arteries were isolated from female Landrace pigs (age = 2 months; N = 27) for wire and pressure myography.

Left ventricle chest compression improves ETCO, blood pressure, and cerebral blood velocity in a swine model of cardiac arrest and cardiopulmonary resuscitation.

Introduction: During cardiopulmonary resuscitation (CPR), high quality chest compressions are critical to organ perfusion, especially the brain. Yet, the optimal location for chest compressions is unclear. It was hypothesized that compared with the standard chest compression (SCC) location, left ventricle chest compressions (LVCCs) would result in greater ETCO, blood pressure (BP), and cerebral blood velocity (CBV) during CPR in swine.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n = 11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n = 9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n = 11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA).

Altered cerebrovascular regulation in low birthweight swine.

Full-term low birthweight (LBW) offspring exhibit peripheral vascular dysfunction in the postnatal period; however, whether such impairments extend to the cerebrovasculature remains to be elucidated. We used a swine model to test the hypothesis that LBW offspring would exhibit cerebrovascular dysfunction at later stages of life. Offspring from 14 sows were identified as normal birthweight (NBW) or LBW and were assessed at 28 (similar to end of infancy) and 56 (similar to childhood) days of age.

Placenta-targeted treatment in hypoxic dams improves maturation and growth of fetal cardiomyocytes in vitro via the release of placental factors.

New Findings: What is the central question of this study? Does treatment of hypoxic dams with a placenta-targeted antioxidant prevent the release of placenta-derived factors that impair maturation or growth of fetal cardiomyocytes in vitro? What is the main finding and its importance? Factors released from hypoxic placentae impaired fetal cardiomyocyte maturation (induced terminal differentiation) and growth (increased cell size) in vitro, which was prevented by maternal treatment with a placenta-targeted antioxidant (nMitoQ). Moreover, there were no sex differences in the effects of placental factors on fetal cardiomyocyte maturation and growth. Overall, our data suggest that treatment targeted against placental oxidative stress could prevent fetal programming of cardiac diseases via the release of placental factors.

Role of Lectin-like Oxidized LDL Receptor-1 and Syncytiotrophoblast Extracellular Vesicles in the Vascular Reactivity of Mouse Uterine Arteries During Pregnancy.

Vascular complications in pregnancy (e.g. preeclampsia) are a major source of maternal and foetal morbidity and mortality, and may be due to excessive release of placental syncytiotrophoblast-derived extracellular vesicles (STBEVs) into the maternal circulation.

Intrauterine exposure to chronic hypoxia in the rat leads to progressive diastolic function and increased aortic stiffness from early postnatal developmental stages.

Aim: We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.

Methods: Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO ) from embryonic day E15-21 or normoxic conditions (controls).

Sex-Specific Effects of Nanoparticle-Encapsulated MitoQ (nMitoQ) Delivery to the Placenta in a Rat Model of Fetal Hypoxia.

Pregnancy complications associated with chronic fetal hypoxia have been linked to the development of adult cardiovascular disease in the offspring. Prenatal hypoxia has been shown to increase placental oxidative stress and impair placental function in a sex-specific manner, thereby affecting fetal development. As oxidative stress is central to placental dysfunction, we developed a placenta-targeted treatment strategy using the antioxidant MitoQ encapsulated into nanoparticles (nMitoQ) to reduce placental oxidative/nitrosative stress and improve placental function without direct drug exposure to the fetus in order to avoid off-target effects during development.

Low altitude simulation without hypoxia improves left ventricular function after myocardial infarction by reducing ventricular afterload.

Humans have a lower risk of death from myocardial infarction (MI) living at low elevations (<2500 m), which are not high enough to induce hypoxia. Both chronic hypoxia pre-MI, achieved by altitude simulation >5000 m, and intermittent hypobaric hypoxia post-MI can reduce MI size in rodents, and it is believed that hypoxia is the key stimulus. To explore mechanisms beyond hypoxia we studied whether altitude simulation <2500 m would also be associated with reduced infarct size.

Alterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries.

Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the angiotensin II type 1 receptor (AT-1).

Sex-specific effects of advanced maternal age on cardiovascular function in aged adult rat offspring.

Pregnancy at an advanced maternal age has an increased risk of complications for both the mothers and their offspring. We have previously shown that advanced maternal age in a rat model leads to poor fetal outcomes, maternal vascular dysfunction, and hypertension, concordant with findings in humans. Moreover, offspring from aged dams had sex-specific cardiovascular dysfunction in young adulthood.

Increased susceptibility to cardiovascular disease in offspring born from dams of advanced maternal age.

Key Points: Advanced maternal age increases the risk of pregnancy complications such as fetal growth restriction, hypertension and premature birth. Offspring born from compromised pregnancies are at increased risk of cardiovascular disease as adults. However, the effect of advanced maternal age on later-onset disease in offspring has not been investigated.

Reduction in Regulatory T Cells in Early Pregnancy Causes Uterine Artery Dysfunction in Mice.

Preeclampsia, fetal growth restriction, and miscarriage remain important causes of maternal and perinatal morbidity and mortality. These complications are associated with reduced numbers of a specialized T lymphocyte subset called regulatory T cells (Treg cells) in the maternal circulation, decidua, and placenta. Treg cells suppress inflammation and prevent maternal immunity toward the fetus, which expresses foreign paternal alloantigens.

Maternal treatment with a placental-targeted antioxidant (MitoQ) impacts offspring cardiovascular function in a rat model of prenatal hypoxia.

Intrauterine growth restriction, a common consequence of prenatal hypoxia, is a leading cause of fetal morbidity and mortality with a significant impact on population health. Hypoxia may increase placental oxidative stress and lead to an abnormal release of placental-derived factors, which are emerging as potential contributors to developmental programming. Nanoparticle-linked drugs are emerging as a novel method to deliver therapeutics targeted to the placenta and avoid risking direct exposure to the fetus.

Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner.

Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease.

Cardiovascular susceptibility to ischemic myocardial injury in male and female rat offspring exposed to prenatal hypoxia.

Intrauterine growth restriction (IUGR) following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease (CVD) in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring, which experienced normoxia (21% O) or hypoxia (11% O) underwent sham or MI surgery at 12 weeks of age.

Prenatal hypoxia and placental oxidative stress: linkages to developmental origins of cardiovascular disease.

Intrauterine growth restriction (IUGR, a pregnancy complication where the fetus does not reach its genetic growth potential) is a leading cause of fetal morbidity and mortality with a significant impact on population health. IUGR is associated with gestational hypoxia; which can lead to placental oxidative stress and fetal programming of cardiovascular disease. Mitochondria are a major source of placental oxidative stress and may provide a therapeutic target to mitigate the detrimental effects of placental oxidative stress on pregnancy outcomes.

Advanced Maternal Age Worsens Postpartum Vascular Function.

The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years.

Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1.

Syncytiotrophoblast extracellular vesicles (STBEVs) are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a multi-ligand scavenger receptor.

Increased heterogeneity of airway calibre in adult rats after hypoxia-induced intrauterine growth restriction.

Background And Objective: Intrauterine growth restriction (IUGR) is associated with asthma development. We hypothesized that IUGR disrupts airway development leading to postnatal structural abnormalities of the airway that predispose to disease. This study therefore examined structural changes to the airway and lung in a rat model of maternal hypoxia-induced IUGR.

Mechanisms of Uterine Artery Dysfunction in Pregnancy Complications.

Pregnancy is a unique condition, and the vascular processes that are required for this undertaking are both complex and extensive. In this review, we discuss the vascular adaptations which occur in the maternal uterine arterial bed to maintain blood supply to the fetal-placental unit. In complicated pregnancies, inadequate remodeling of the uterine arteries, hormonal imbalances, and pre-existing conditions such as obesity, hypertension, diabetes etc.

Postnatal resveratrol supplementation improves cardiovascular function in male and female intrauterine growth restricted offspring.

Intrauterine growth restriction (IUGR) may predispose offspring to an increased susceptibility of developing cardiovascular disease (CVD) in adult life. The window of opportunity to treat later life CVD programmed in fetal life is critical. The aim of this study was to identify the effect of resveratrol treatment of IUGR offspring at a time of known CV dysfunction.

Loss of smooth muscle cell disintegrin and metalloproteinase 17 transiently suppresses angiotensin II-induced hypertension and end-organ damage.

Hypertension is associated with hypertrophy and hyperplasia of smooth muscle cells (SMCs). Disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme reported to mediate SMC hypertrophy through activation of epidermal growth factor receptor (EGFR). We investigated the role of ADAM17 in Ang II-induced hypertension and end-organ damage.