Rats with hypertension induced by in utero exposure to maternal low-protein diets fail to increase blood pressure in response to a high salt intake.
TL;DR: Rats with maternal-diet-induced hypertension appear to be insensitive to the hypertensive effects of sodium chloride, and this insensitivity does not appear to stem from a more rapid clearance of excess sodium, and may relate to other aspects of kidney function and metabolism.
Abstract: Hypertension in the rat has been demonstrated to be determined in utero by exposure to maternal low-protein diets. Assessment was made of the response of rats with maternal diet-induced hypertension to a chronic high intake of sodium chloride. Normotensive and hypertensive animals were provided with either drinking water (control) or 1.5% sodium chloride over a 7-day period. Normotensive rats significantly increased blood pressure in response to the increased salt intake. 5-7 days after the start of the study systolic blood pressure was 30-41 mm Hg higher than in controls. 7 days of salt drinking did not alter blood pressure in maternal low-protein diet-exposed, hypertensive rats. In both normotensive and hypertensive groups provision of 1.5% sodium chloride significantly increased fluid intake. In hypertensive rats the increased fluid intake appeared to be an immediate response, whilst normotensive rats increased intake only after the first day. Urinary volume was increased in both groups of animals receiving salt, within 1 day, and Na + excretion similarly increased by between 3.5- and 4.5-fold in both groups. K + excretion initially decreased significantly in both normotensive and hypertensive rats drinking 1.5% sodium chloride, but returned to pre-salt drinking levels by day 5 of the experiment. Rats with maternal-diet-induced hypertension appear to be insensitive to the hypertensive effects of sodium chloride. This insensitivity does not appear to stem from a more rapid clearance of excess sodium, and may relate to other aspects of kidney function and metabolism.
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TL;DR: Whether the metabolic syndrome can be reliably induced by the interventions made is assessed and the validity of the different species, diets, feeding regimes and end‐point measures used is discussed.
Abstract: The incidence of the metabolic syndrome, a cluster of abnormalities focusing on insulin resistance and associated with high risk for cardiovascular disease and diabetes, is reaching epidemic proportions. Prevalent in both developed and developing countries, the metabolic syndrome has largely been attributed to altered dietary and lifestyle factors that favour the development of central obesity. However, population-based studies have suggested that predisposition to the metabolic syndrome may be acquired very early in development through inappropriate fetal or neonatal nutrition. Further evidence for developmental programming of the metabolic syndrome has now been suggested by animal studies in which the fetal environment has been manipulated through altered maternal dietary intake or modification of uterine artery blood flow. This review examines these studies and assesses whether the metabolic syndrome can be reliably induced by the interventions made. The validity of the different species, diets, feeding regimes and end-point measures used is also discussed.
547 citations
Cites background from "Rats with hypertension induced by i..."
...Langley-Evans & Jackson (1996) demonstrated that sodium loading offspring of protein deprived dams did not result in further increases in blood pressure, suggesting that those animals did not have a shifted pressure–natriuresis curve....
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TL;DR: The window of sensitivity of adult blood pressure to prenatal protein restriction falls within the period of nephrogenesis in the rat, consistent with the hypothesis that maternal protein restriction causes adult hypertension in the offspring through impairment of renal development.
356 citations
Cites result from "Rats with hypertension induced by i..."
...In contrast to our present findings, Langley-Evans and Jackson [25] reported that hypertensive adult offspring of protein-restricted mothers did not increase blood pressure further when sodium intake was increased....
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TL;DR: Dietary protein restriction in pregnancy induces hypertension and vascular dysfunction in male offspring, and abnormalities in the nitric oxide-cGMP pathway may explain the defect in endothelium-dependent and -independent relaxation.
Abstract: It is established that dietary protein restriction of pregnant rats results in their offspring developing hypertension. However, to date no studies have investigated peripheral vascular function of offspring using the low protein model. Therefore, the aim of the study was to assess isolated resistance artery function from adult male offspring of control (C, 18% casein) and protein-restricted (PR, 9% casein) pregnant dams at two different ages. The birthweight of PR offspring did not significantly differ from that of C offspring. Systolic blood pressure was significantly elevated in PR compared with C (p < 0.05). Maximal vascular contraction to phenylephrine and the thromboxane analog U46619 were similar in C and PR offspring at postnatal d 87 and 164. Relaxation induced by the endothelium-dependent vasodilators acetylcholine or bradykinin was significantly reduced in the PR group (p < 0.05). Relaxation to the endothelium-independent vasodilator sodium nitroprusside and phosphodiesterase type 3 inhibitor cilostamide was less in the PR offspring compared with C (p < 0.01). Dietary protein restriction in pregnancy induces hypertension and vascular dysfunction in male offspring. Abnormalities in the nitric oxide-cGMP pathway may explain the defect in endothelium-dependent and -independent relaxation. Reduced vasodilation may be a potential mechanism underlying the elevated systolic blood pressure observed in this model.
247 citations
TL;DR: The age-dependent interactions of principal systems controlling the structure and function of the cardiovascular system in immature rats developing hypertension are outlined and critical periods (developmental windows) should be respected in the future pharmacological or gene therapy of human hypertension.
Abstract: In this review, we attempt to outline the age-dependent interactions of principal systems controlling the structure and function of the cardiovascular system in immature rats developing hypertensio...
226 citations
Cites background from "Rats with hypertension induced by i..."
...Blood pressure increase induced by prenatal protein malnutrition is not enhanced by a high salt intake (410) or by diets supplemented with saturated fatty acids (406)....
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TL;DR: It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation of rats.
Abstract: Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (CON; n 10) or MLP (n 10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F1 generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure produced an F3 generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F1 generation MLP-exposed offspring exhibited raised (P < 0.001) systolic blood pressure (male 143 (sem 4) mmHg; female 141 (sem 4) mmHg) compared with CON animals (male 132 (sem 3) mmHg; female 134 (sem 4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F2 generation (P < 0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (MLP x CON, CON x MLP and MLP x MLP) were hypertensive (132 (sem 3) mmHg) compared with CON animals (CON x CON; 123 (sem 2) mmHg). No effect was noted in the F3 generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation.
162 citations