Mechanisms underlying the programming of small artery dysfunction: review of the model using low protein diet in...

Area of Science:

• Reproductive biology
• Vascular physiology
• Developmental programming

Background:

• Maternal nutrition significantly influences offspring's long-term health, particularly cardiovascular and metabolic disease risk.
• The Southampton maternal low protein (SMLP) model demonstrates that protein deprivation during pregnancy elevates offspring blood pressure.
• Impaired peripheral arterial function is a potential mechanism underlying cardiovascular dysfunction in SMLP offspring.

Purpose of the Study:

• To review the impact of maternal low protein diet on vascular resistance artery function across multiple generations.
• To investigate the role of endothelial nitric oxide signaling in programmed vascular adaptations.

Main Methods:

• Utilized the Southampton maternal low protein (SMLP) rat model.
• Examined vascular function in resistance arteries from pregnant dams, offspring (F1), pregnant offspring (pF1), and second-generation offspring (F2).
• Assessed endothelium-dependent relaxation and implicated nitric oxide-guanylate cyclase signaling.

Main Results:

• Disturbances in endothelium-dependent relaxation were observed at all examined generational stages (pF(o), F(1), pF(1), F(2)).
• Maternal protein deprivation leads to persistent vascular dysfunction across generations.
• Evidence suggests alterations in the nitric oxide-guanylate cyclase pathway contribute to these programmed effects.

Conclusions:

• Maternal low protein diet induces lasting vascular dysfunction and hypertension in offspring, extending to subsequent generations.
• The nitric oxide-guanylate cyclase signaling pathway is critically involved in the vascular adaptations to pregnancy and developmental programming.
• This model highlights the profound impact of early-life nutrition on cardiovascular health across the lifespan.