Changes to the maternal cardiovascular system during pregnancy include an increase in the release of nitric oxide (NO) (Nathan et al. 1995) and endothelial-derived hyperpolarising factor (EDHF) (Gerber et al. 1998). A reduction in these in the resistance circulation may lead to pregnancy complications. In the rat, restriction of dietary protein in pregnancy results in hypertensive offspring (Langley & Jackson, 1994) and also causes vascular endothelial dysfunction in the mesenteric (Koumentaki et al. 2001) and uterine arteries (Itoh et al. 2001) of pregnant dams. The aim of this study was to assess the effect of protein restriction in pregnant dams on β-adrenoceptor-mediated vasodilatation.
All procedures were carried out according to UK legislation. Virgin female Wistar rats were fed on a control (C; 18 % casein) or on a protein-restricted (PR; 9 % casein) diet throughout pregnancy. The pregnancy was terminated on day 18/19 of gestation by CO2 inhalation and cervical dislocation. Mesenteric arteries were dissected (mean diameter ~276 µm), mounted on a wire myograph bathed in PSS at 37 °C and gassed with 5 % CO2 and 95 % O2. Following normalisation, concentration response curves to phenylephrine (PE; 10 nM-100 µM), acetylcholine (ACh; 1 nM-100 µM) and isoprenaline (Iso; 1 nM-100 µM) were carried out. Data are expressed as means ± S.E.M., and differences were calculated by Student’s unpaired t test with 95 % confidence intervals.
Sensitivity to the endothelium-dependent vasodilator, ACh, was significantly decreased in the PR group with no change in the maximum relaxation (-log EC50: C, 8.2 ± 0.1, n = 6; PR, 7.8 ± 0.1, n = 7, P < 0.05). Vasodilatation to the β-adrenoceptor agonist, Iso, was significantly attenuated in the PR group (-log EC50: C, 8.3 ± 0.1, n = 7; PR, 7.9 ± 0.1, n = 8, P < 0.05; % maximum response: C, 90 ± 3, n = 7; PR, 77 ± 3, n = 8, P < 0.01). Sensitivity to the vasoconstrictor PE was also increased in the PR group with no increase in the maximum (-log EC50: C, 5.7 ± 0.02, n = 8; PR, 5.8 ± 0.02, n = 9, P < 0.05).
In conclusion maternal protein restriction during pregnancy alters the vasoreactivity of isolated small mesenteric arteries.
This work is supported by the British Heart Foundation.