Hypercaloric Diet Induces Cardiovascular Dysfunction Through Altered Purinergic Signaling on Atrial and Vascular...

Area of Science:

• Cardiovascular Physiology
• Metabolic Disorders
• Purinergic Signaling

Background:

• Obesity and hypercaloric diets are linked to cardiovascular dysfunction, diabetes, and hypertension, often mediated by sympathetic nervous system hyperactivity.
• Purinergic signaling, involving adenosine and ATP, is a key modulator of cardiovascular function, but its role in diet-induced dysfunction is not fully understood.

Purpose of the Study:

• To investigate the impact of a hypercaloric diet on metabolic parameters, atrial purinergic signaling, and vascular reactivity in rats.
• To elucidate the specific mechanisms by which purinergic pathways are altered in diet-induced cardiometabolic dysfunction.

Main Methods:

• Rats were fed a hypercaloric diet for 8 weeks, with measurements of body weight, visceral adiposity, systolic blood pressure, cardiac hypertrophy, glucose levels, and insulin sensitivity.
• Isolated right and left atria and thoracic aorta were used to assess contractile function and vascular responsiveness to purinergic agonists.

Main Results:

• Hypercaloric diet led to increased body weight, visceral adiposity, systolic blood pressure, and cardiac hypertrophy, with altered glucose and insulin levels.
• In isolated atria, the diet increased basal contractile force and altered the biphasic response to ATP, reducing the negative inotropic effect (NIE) and enhancing the positive inotropic effect (PIE).
• Vascular studies showed impaired adenosine-mediated relaxation and increased contraction, indicating hyperreactivity.

Conclusions:

• A hypercaloric diet induces cardiometabolic dysfunction, characterized by impaired cardiovascular function and altered purinergic signaling (P1/P2 pathways).
• These purinergic alterations contribute to obesity-associated cardiovascular remodeling and hypertension, highlighting a novel therapeutic target.