a1 Maternal, Fetal and Neonatal Physiology, Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
a2 Division of Reproduction and Endocrinology, King's College London, London SE1 7EH, UK
We have previously demonstrated that maternal protein restriction during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring (F1). Here we show that these characteristics are transmitted to the F2 offspring through the maternal line, in the absence of any additional challenges to the F1. Female Wistar rats were fed either a control (18 % casein) or protein-restricted diet (PR; 9 % casein) throughout pregnancy. Female F1 offspring, maintained on standard chow postpartum, were mated with breeding males to produce F2 progeny. Systolic blood pressure (SBP) in male F2 offspring was assessed by tail-cuff plethysmography at age 100 d and vascular function of small mesenteric arteries by wire myography at age 80 and 200 d. SBP was raised in PR F2 offspring compared with controls (control 122·1 (sem 2·3) mmHg, n 7; PR 134·7 (sem 3·2) mmHg, n 6; P < 0·01) and endothelial function, assessed by vasodilatation to acetylcholine, was impaired at both age 80 d (% maximal response: control 89·7 (sem 2·6), n 14; PR 72·7 (sem 4·4), n 15; P < 0·01) and 200 d (effective concentration equal to 50 % of maximum (pEC50): control 7·67 (sem 0·10), n 10; PR 7·33 (sem 0·07), n 8; P < 0·05). The present study demonstrates that both raised blood pressure and endothelial dysfunction are passed via the maternal line to grand-offspring in the absence of any additional dietary challenges to their F1 mothers. Risk factors for chronic disease may therefore be heritable by non-genomic processes.
(Received July 24 2007)
(Revised December 04 2007)
(Accepted January 02 2008)
(Online publication February 28 2008)
Abbreviations: ACh, acetylcholine; INDO, indomethacin; PSS, physiological salt solution; l-NAME, Nω-nitro-l-arginine methyl ester; PE, phenylephrine; pEC50, effective concentration equal to 50 % of maximum; PR, protein-restricted diet