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  • Print publication year: 2006
  • Online publication date: August 2009

21 - The role of vascular dysfunction in developmental origins of health and disease: evidence from human and animal studies

Summary

Introduction

Early studies in population cohorts proposed that perturbation of the environment in utero and in early life gives rise to marked and permanent alteration in offspring cardiovascular homeostasis, leading to increased risk of cardiovascular and metabolic disease in later life (reviewed in this volume). Clinical outcomes focused on the incidence of heart disease and hypertension in relation to birthweight, with little detailed investigation of other parameters of cardiovascular risk or outcome. More recent studies have given insight into underlying aetiological pathways, and the development of the different animal models of developmental plasticity has provided an opportunity to assess parameters of cardiovascular function at a depth which is not feasible, or indeed practicable, in humans.

The mechanisms contributing to cardiovascular homeostasis are complex and interwoven; they range from central control of the heart rate and vascular tone to paracrine, autocrine and genomic influences on the vascular smooth muscle and function of the endothelium. Fluid and volume homeostatic pathways, as well as the intricacy of haemostatic control, also contribute to the status quo. The complexity is such that common disorders such as essential hypertension remain poorly understood despite decades of research. The scientist wishing to investigate developmental programming of, for example, metabolic syndrome faces a bewildering choice of avenues to explore. Without a firm understanding of the early aetiology of hypertension or of insulin resistance, he or she has little choice but to follow the well-trodden paths which characterise research into these disorders in humans.

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