|Steeds RP et al.|
Altered Coronary Arterial Reactivity Following Pharmacological Perinatal Interventions
Journal of Clinical and Basic Cardiology 2002; 5 (1): 109-114
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Keywords: Geburtsgewicht, koronar-arterielle Reaktivitšt, perinatal, Programmierung, birth weight, coronary artery reactivity, perinatal, programming
The Barker hypothesis proposes that the risk of ischaemic heart disease may be increased in later life by perinatal events that programme permanent alterations to the body's structure and metabolism. Perinatal modification of arterial compliance and function could initiate and amplify this risk of disease in later life. The aim of this study was to determine whether short-term nitric oxide synthase (NOS) inhibition and transient hypoxia in the perinatal period could initiate changes in vasomotility demonstrable in later life. Dams were given Ng-nitro-L-arginine methyl ester (n = 5) in drinking water or were kept in a normobaric hypoxic chamber (FiO2 10 %) for one week pre- and one week post-partum. Male offspring were sacrificed at 10 weeks and results compared with the male offspring of control dams (n = 7). Coronary artery reactivity, to both constrictors and dilators, was studied using the wire myograph and isolated blood perfused heart preparations. Perinatal inhibition of NOS increased the contractile response of coronary arteries in adulthood in both isolated vessels and in perfused heart preparations without a change in dilator responses to ACh and hypoxia. These differences were not associated with changes in arterial compliance and body weight. Perinatal hypoxia enhanced the vasodilatation to hypoxia in adulthood in perfused heart preparations with a reduction in vasodilatation to ACh. These differences were associated with a reduction in body growth, a shift in the pressure-flow relationship indicative of vascular remodeling and evidence of right ventricular hypertrophy. It is concluded that short-term perinatal insults may alter coronary arterial reactivity in adulthood independent of an effect of birth weight. Perinatal modification of arterial function may be one mode by which risk of disease in later life may be initiated or amplified.