ABSTRACT
OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.
Subject(s)
Animals , Female , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Sleep Deprivation/complications , Hypertension/etiology , Kidney Diseases/etiology , Prenatal Exposure Delayed Effects/physiopathology , Sleep Deprivation/physiopathology , Autonomic Nervous System/physiopathology , Time Factors , Blood Pressure/physiology , Random Allocation , Risk Factors , Rats, Wistar , Baroreflex/physiology , Fetal Development/physiology , Disease Models, Animal , Fourier Analysis , Glomerular Filtration Rate , Heart Rate/physiology , Hypertension/physiopathology , Kidney/physiopathology , Kidney Diseases/physiopathologyABSTRACT
La vasculogénesis es controlada por una serie de mecanismos que se activan en función del tiempo y del espacio durante el desarrollo embrionario. Múltiples son las vías de señalización implicadas en las etapas del proceso vasculogénico, las que se inician con estímulos angiogénicos desde el mesodermo o desde el endodermo para dar origen a los angioblastos (células progenitoras endoteliales). Proteínas como el factor de crecimiento vascular endotelial (VEGF), factor de crecimiento fibroblastico 2 (FGF2), entre otras, constituyen factores claves en la inducción de este proceso. Posteriormente, los angioblastos deben migrar para dar origen a los vasos primitivos, proceso en el que participan factores atrayentes y repulsivos que orientarán la dirección de su migración. Adicionalmente, los mecanismos de diferenciación arterio-venosa, regulados por la vía de señalización Hedgegog, VEGF y Notch, son determinados antes del inicio de la circulación, lo que sugiere que el destino de la célula endotelial se encuentra genéticamente determinado. Por su parte, los procesos de remodelación y proliferación vascular post natal, son generados a través de la formación de nuevos vasos a partir de vasos pre existentes (angiogénesis). El factor angiogénico que induce los cambios morfológicos y funcionales en las células endoteliales es el VEGFA, las cuales, adquieren la capacidad de direccionar al nuevo vaso en desarrollo. Uno de los principales estímulos físicos que modifica el patrón de crecimiento de los lechos vasculares es el estrés de flujo, el cual, es susceptible de ser modificado por situaciones de estrés como el ejercicio físico. En la presente revisión, se abordan los principales mecanismos implicados en la regulación fisiológica de la vasculogénesis y angiogénesis. Adicionalmente, se discutirán los mecanismos que sustentan la respuesta vascular inducida por estrés de flujo, considerando su rol en el establecimiento de los patrones de crecimiento vascular.
Vasculogenesis is controlled by a number of mechanisms that are activated as a function of time and space during embryonic development. Multiple signaling pathways are involved in the stages of vasculogenic process, which start with angiogenic stimuli from the mesoderm or the endoderm to give rise to angioblasts (endothelial progenitor cells). Proteins such as vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), among others, are key factors in the induction of this process. Subsequently, the angioblasts must migrate to give birth to primitive vessels, a process that involves attractive and repulsive factors that guide the direction of their migration. Additionally, arterial and venous differentiation regulated hedgegog signaling pathway, VEGF and Notch are determined before the start of circulation, suggesting that the endothelial cell fate is determined genetically. On the other hand, the processes of remodeling and postnatal vascular proliferation are generated through the formation of new vessels from pre-existing vessels (angiogenesis). The angiogenic factor that induces morphological and functional changes in the endothelial cells is the VEGFA, these vessels acquire the ability to address the new developing vessel. One of the main physical stimuli that modify the growth pattern of the vascular beds is the shear stress, which is modified by exercise. In this review, the main mechanisms involved in the physiological regulation of vasculogenesis and angiogenesis are addressed. Additionally, the mechanisms underlying the vascular response induced by shear stress will be discussed, considering its role in establishing patterns of vascular growth.
Subject(s)
Humans , Angiogenesis Modulating Agents , Endothelial Cells/physiology , Neovascularization, Physiologic/physiology , Exercise , Stress, MechanicalABSTRACT
Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.
Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.