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Timothy Wheeler

Publications and source records attributed to Timothy Wheeler.

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Vasodilation to vascular endothelial growth factor in the uterine artery of the pregnant rat is blunted by low dietary protein intake.

Pregnancy is associated with a substantial increase in uterine artery blood flow, which may in part result from dilation in response to vascular endothelial growth factor (VEGF). Uterine blood flow is reported to be reduced in globally diet-restricted pregnant rats. Both global and protein dietary restriction in pregnancy produce programmed effects in offspring. In this study we hypothesized that protein restriction in pregnancy impairs maternal uterine artery responses to VEGF. Vascular responses to VEGF were determined in isolated uterine arteries of pregnant (18 or 19 d of gestation) Wistar rats fed a diet containing either 18% or 9% casein throughout pregnancy. For comparison, responses to phenylephrine, potassium chloride, and acetylcholine were determined. In addition, the response of the mesenteric artery to VEGF was studied in the same animals. A significant reduction of the maximal relaxation to VEGF (p = 0.041) and in the overall response (p = 0.004) to VEGF was found in uterine arteries of the 9% compared with the 18% group, but responses to all other agonists were similar. The VEGF response was reduced by cyclooxygenase inhibition (indomethacin) in both groups. In the 18%, but not the 9%, group it was further reduced by nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester). VEGF was shown to dilate the mesenteric artery but this effect was not significantly altered by the low-protein diet. These results show an attenuated uterine artery vasodilator response to VEGF produced by a low-protein diet in pregnancy, partly because of a reduction of the nitric oxide component of VEGF-mediated relaxation.

Acetylcholine↗

Low-protein diet impairs vascular relaxation in virgin and pregnant rats.

Pregnancy is associated with increases in maternal cardiac output and plasma volume and a reduction in peripheral vascular resistance. Cardiac output and plasma volume are substantially reduced in pregnant rats fed a low-protein diet, but it is not known whether vascular function is also compromised. We have investigated vascular function in virgin and pregnant Wistar rats subjected to dietary protein restriction [9% (w/v) casein, compared with 18% (w/v) casein for controls]. The diets were fed to the groups for 18 days; in the pregnant rats, the diets were given from day 1 of pregnancy. Branches of the mesenteric arteries were studied on day 18 of the dietary period using myography. Significant reductions in sensitivity to acetylcholine occurred in vessels from virgin (P=0.04) and pregnant (P=0.01) rats that had consumed the 9% casein diet. In arteries from the virgin rats on the restricted diet there was also a significant reduction in sensitivity (P=0.0003) and maximum relaxation (P=0.009) to the NO donor spermine NONOate. Mean placental and fetal weights were significantly lower in the rats fed on 9% casein (P<0.0001 and P=0.005 respectively). Thus low-protein diets impair vasodilator responses in female rats. These effects may contribute to the poor cardiovascular adaptation to pregnancy and lower fetal weights associated with restricted protein intake.

Acetylcholine↗