Methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in spontaneously hypertensive...

Area of Science:

• Cardiovascular Research
• Metabolic Disease Research
• Vascular Biology

Background:

• Methylglyoxal (MGO), a glucose metabolite, is implicated in diabetes-related macrovascular complications like hypertension.
• Elevated MGO levels may contribute to vascular dysfunction and increased blood pressure.

Purpose of the Study:

• To investigate the role of MGO accumulation in the vascular reactivity of mesenteric arteries from spontaneously hypertensive rats (SHR).
• To determine if MGO scavenging with aminoguanidine (AG) can ameliorate hypertension-related vascular changes in SHR.

Main Methods:

• SHR were treated with aminoguanidine (AG) for 5 weeks to assess its effects on blood pressure and MGO-derived advanced glycation end-products.
• Vascular reactivity, including acetylcholine-induced relaxation and angiotensin II-induced contraction, was evaluated in isolated mesenteric arteries.
• Reactive oxygen species (ROS) production, NADPH oxidase (NOX) expression, and Angiotensin II type 2 receptor (AT2R) expression were analyzed.

Main Results:

• AG treatment partially normalized blood pressure in SHR and reduced MGO-derived advanced glycation end-products in mesenteric arteries.
• AG normalized impaired endothelium-dependent relaxation and reduced exaggerated angiotensin II-induced contraction in SHR mesenteric arteries.
• Increased ROS production, NOX1, and AT2R expression in SHR mesenteric arteries were normalized by AG; AT2R blockade, not NOX inhibition, reversed Ang II-induced contraction.

Conclusions:

• MGO accumulation in mesenteric arteries contributes to hypertension development in SHR.
• MGO exacerbates hypertension partly through increased ROS-mediated impairment of endothelium-dependent relaxation.
• MGO also contributes to hypertension via AT2R-mediated potentiation of angiotensin II-induced contraction.