Developmental Conditioning of the Vasculature

Abstract

There is increasing evidence from epidemiological and experimental animal studies that the early life environment, of which nutrition is a key component, acts through developmental adaptive responses to set the capacity of cardiovascular and metabolic pathways to respond to physiological and pathophysiological challenges in later life. One finding that is consistent to both population studies and animal models is the propensity for such effects to induce endothelial dysfunction throughout the vascular tree, including the microvasculature. Obesity, type 2 diabetes and hypertension are associated with changes in microvascular function affecting multiple tissues and organs. These changes may be detected early, often before the onset of macrovascular disease and the development of end organ damage. Suboptimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity in the offspring, which together with microvascular rarefaction and remodeling serve to limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates; they also increase local and overall peripheral resistance. This article explores how a developmentally conditioned disadvantageous microvascular phenotype may represent an important and additional risk factor for increased susceptibility to the development of cardio-metabolic disease in adult life and considers the cell signaling pathways associated with microvascular dysfunction that may be "primed" by the maternal environment. As the microvasculature has been shown to be a potential target for early therapeutic and lifestyle intervention, this article also considers evidence for the efficacy of such strategies in humans and in animal models of the developmental origins of health and disease.

Coronary and muscle blood flow during physical exercise in humans; heterogenic alliance

“…For example, NO mediates vascular relaxation of 327 relatively large, conduit arteries, whereas endothelium-derived 328 hyperpolarization factors (EDHF) play a crucial role in the 329 relaxation of small (resistant) arteries [69]. 330 One of the major stimuli linked to exercise-induced vasodila-331 tion is shear stress, a frictional force along endothelial cell 332 membranes exerted by blood flow [70].…”

Uteroplacental insufficiency temporally exacerbates salt‐induced hypertension associated with a reduced natriuretic response in male rat offspring

“…The vasculature is sensitive to perturbations in the early‐life environment and adaptations made in this system can predispose to later cardiovascular disease (Clough, ). In the present study, passive stiffness of mesenteric and renal arteries was not different between Control and Restricted male offspring.…”

“…, ; White et al . ; Clough, ). Uteroplacental insufficiency is the most common cause of fetal growth restriction in Western nations and affects around one in ten pregnancies (Henriksen & Clausen, ).…”

Altered post‐capillary and collecting venular reactivity in skeletal muscle with metabolic syndrome

“…Further, it was recently suggested that the pro‐inflammatory and pro‐oxidant conditions observed in post‐capillary venules may be the initiating site for microvascular rarefaction that is commonly associated with chronic metabolic disease (Gilbert, ; Frisbee et al . ; Clough, ) and that fluid handling across the microcirculation may be altered by chronic impairments to glycaemic control (Huxley & Scallan, ; Scallan et al . ).…”