Title:
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Dietary influence on maternal vascular function in pregnancy in the rat
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Pregnancy is a state characterized by significant cardiovascular adaptive responses to meet the metabolic needs of the mother and fetus. Maternal blood volume and cardiac output are increased, while total vascular resistance and arterial pressure tend to decrease. Maternal cardiac output and plasma volume are substantially reduced in pregnant rats fed a low protein diet or fed 50% of their normal daily food intake throughout gestation, but it is not known whether vascular fimction is also compromised. This thesis investigates the effect of a low protein diet (9% casein) on systemic nitric oxide production and vascular function in virgin and pregnant rats. Systemic nitric oxide (NO) production was assessed through urinary nitrate excretion. Urinary nitrate excretion was reduced on day 18 of gestation on the low protein diet {P = 0.04), although overall the data were inconclusive. To investigate the influence of a 9% casein diet on vascular reactivity, contractile responses to phenylephrine (PE), or acetylcholine (ACh)-mediated relaxation and the contribution of NO to these mechanisms were studied in virgin and pregnant rats. Virgin and pregnant Wistar rats were fed either the 18% casein or 9% casein diets for 18-19 days; in the pregnant rats, the diets were given A-om day 1 of pregnancy. 3 mm segments of a third-order mesenteric artery (- 300 ^im in diameter) were excised and mounted on fine tungsten wires on a small vessel myograph. There were no di^erences in contractile sensitivity to PE in these vessels G-om virgin (f = 0.6) and pregnant rats (f = 0.3) fed the 18% casein and the 9% casein diet. Significant reductions in the sensitivity to ACh were found in vessels &om virgin (f = 0.03) and pregnant (f ^ 0.02) rats that had consumed the 9% casein diet. Inhibition of cyclooxygenase and NO synthesis with a combination of indomethacin (ESfDO) and N^-nitro-L-arginine methyl ester (L-NAME) significantly decreased ACh-induced dilations in all groups, whereas indomethacin alone did not affect the ACh response. In arteries from the virgin rats on the low protein diet there was also a signiGcant reduction in the sensitivity (f = 0.0003) and maximum relaxation (f - 0.009) to the NO donor spermine NONOate (SPN) whereas the vasodilator potency of SPN did not differ between pregnant 18% and 9% casein-fed rats. Mean placental and fetal weights were significantly lower in the rats fed on 9% casein {P < 0,0001 and P = 0.005 respectively). The results show that 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.
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