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Effects of maternal protein restriction on central and peripheral renin-angiotensin systems in male rat offspring
Monique Assis de Vasconcelos Barros1, José Luiz de Brito Alves2, Rayssa Gabriella Nery Barros3
1Laboratory of Nutrition, Physical Activity and Phenotypic Plasticity, Academic Center of Vitoria (CAV), Federal University of Pernambuco, 55608-680 Vitória de Santo Antão, Brazil; Graduate Program in Nutrition, Health Sciences Center, Federal University of Pernambuco, UFPE, 50670-901, Recife, Brazil; Carmen (Cardiology, Metabolism and Nutrition) Laboratory, INSERM U1060, Lyon-1 University, South Lyon Medical Faculty, 69921 Oullins, France.
Insights
Maternal low-protein diet induces arterial hypertension in male offspring rats. The renin-angiotensin system (RAS) contributes peripherally, not centrally, to this condition, impacting cardiorespiratory control.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Nutritional Science
Background:
- Maternal dietary protein intake critically influences offspring development and long-term health.
- The renin-angiotensin system (RAS) plays a key role in regulating blood pressure and cardiovascular function.
- Nutritional programming during gestation can lead to persistent alterations in offspring physiology.
Purpose of the Study:
- To investigate the role of the renin-angiotensin system (RAS) in cardiorespiratory control of male offspring from dams fed a low-protein diet.
- To determine whether central or peripheral RAS activation contributes to hypertension in offspring exposed to maternal protein restriction.
Main Methods:
- Male offspring from normoprotein (NP) and low-protein (LP) diet dams were studied.
- Arterial pressure (AP), heart rate (HR), and respiratory frequency (RF) were measured at rest and after central (ICV) or peripheral (IV) administration of losartan.
- Cardiovascular variability, peripheral chemoreflex sensitivity, and gene expression (Rac1, MAPK) were assessed.
Main Results:
- LP offspring exhibited higher mean AP and RF compared to NP offspring.
- Central losartan administration did not normalize AP or RF in LP rats, while peripheral losartan caused a greater reduction in MAP in LP rats.
- LP rats showed reduced gene expression of Rac1 and similar peripheral chemoreflex sensitivity compared to NP rats.
Conclusions:
- The RAS is involved peripherally, not centrally, in maintaining elevated blood pressure in male offspring of protein-restricted dams.
- Maternal protein restriction induces hypertension in offspring, mediated by peripheral RAS components.
- These findings highlight the impact of maternal nutrition on offspring cardiovascular health via RAS pathways.
Aims:
We investigated the involvement of the renin angiotensin system (RAS) on the cardiorespiratory control in rats from dams fed with a low-protein diet.
Main Methods:
Male offspring were obtained from dams fed a normoprotein diet (NP, 17% casein) and low-protein diet (LP, 8% casein) during pregnancy and lactation. Direct measurements of arterial pressure (AP), heart rate (HR) and respiratory frequency (RF) were recorded in awake 90-day-old at resting and after losartan potassium through either intracerebroventricular (ICV) microinjections or intravenous (IV) administration. Cardiovascular variability was evaluated by spectral analysis. Peripheral chemoreflex sensitivity was assessed through the potassium cyanide (KCN; 40 μg/0.1 ml/rat, IV). Gene expression was evaluated by qPCR, and MAPK (Mitogen Activated Protein Kinase) expression was evaluated by western blot.
Key Findings:
The LP offspring had higher mean AP (MAP) and RF than NP offspring. In the spectral analysis, the LP rats also showed higher low frequency of systolic AP (NP: 2.7 ± 0.3 vs. LP: 5.0 ± 1.0 mmHg). After ICV losartan, MAP and RF in LP rats remained higher than those in NP rats, but without changes in HR. The peripheral chemoreflex was similar between the groups. LP group had lower gene expression of Rac1 (Ras-related C3 botulinum toxin substrate 1) (NP: 1.13 ± 0.06 vs. LP: 0.88 ± 0.08). Peripherally, LP rats had larger delta of MAP after IV losartan (NP: -9.8 ± 2 vs. LP: -23 ± 6 mmHg), without changes in HR and RF.
Significance:
In rats, the RAS participates peripherally, but not centrally, in the maintenance of arterial hypertension in male offspring induced by maternal protein restriction.
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