First evidence for transgenerational vascular programming in the rat protein restriction model

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University of Central Lancashire / University of Liverpool (2002) J Physiol 543P, S013

Communications: First evidence for transgenerational vascular programming in the rat protein restriction model

C. Torrens*, L. Brawley*, C.S. Dance*, S. Itoh*, L. Poston† and M.A. Hanson*

*Centre for Fetal Origins of Adult Disease, University of Southampton, Southampton SO16 5YA and †Maternal & Fetal Research Unit, Guy's, King's & St Thomas' Hospitals, London SE1 7EH, UK

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Human epidemiological studies have shown a link between poor maternal nutrition and cardiovascular disease in later life (Roseboom et al. 2001). Previous studies have shown in rats that restriction of dietary protein in pregnancy causes maternal vascular dysfunction (Itoh et al. 2002; Koumentaki et al. 2002) and results in offspring with raised blood pressure (Langley & Jackson, 1994) and vascular dysfunction (Brawley et al. 2002), which is also apparent in pregnant offspring (Torrens et al. 2002). However, no studies have investigated the effect of protein restriction during pregnancy on second generation (F2) offspring.

First generation female offspring of previously unmated Wistar rats, which had been fed a control (C; 18 % casein) or a protein-restricted (PR; 9 % casein) diet throughout pregnancy, were mated at around 100 days of age (approximately 200 g body weight). Male F2 offspring were humanely killed by CO2 inhalation and cervical dislocation at ca 80 days of age. Small mesenteric arteries were mounted on a wire myograph, bathed in PSS at 37 °C and continually gassed with 95 % O2 and 5 % CO2. Following normalisation, concentrationÐresponse curves to phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) were carried out. Data are expressed as means ± S.E.M., and significance tested by Student’s unpaired t test.

Sensitivity to PE was increased in the PR group with no increase in the maximum (-log EC50: C, 5.87 ± 0.04, n = 13; PR, 6.06 ± 0.03, n = 15; P < 0.001; % maximal response: C, 119 ± 2, n = 13; PR, 122 ± 2, n = 15; P = 0.27). Vasodilatation to ACh was attenuated in the PR group (ACh; % maximal response: C, 90 ± 3, n = 14; PR, 73 ± 4, n = 15, P < 0.01). The maximal response to SNP was enhanced in the PR group (SNP; % maximal response: C, 77.3 ± 3.3, n = 14; PR, 87.5 ± 2.4, n = 9, P < 0.05).

In conclusion maternal protein restriction during pregnancy causes vascular dysfunction in the second generation even in the absence of additional nutritional challenges. These findings differ in some respects from those seen in the previous generation (Brawley et al. 2002), but offer a new insight into vascular programming.

This work is supported by the British Heart Foundation.

All procedures accord with current UK legislation.

Where applicable, experiments conform with Society ethical requirements.

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