Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates.

Area of Science:

• Physiology
• Metabolic Disorders
• Vascular Biology

Background:

• Insulin resistance (IR) is linked to impaired capillary blood volume (CBV) augmentation, potentially limiting glucose uptake.
• Understanding early mechanisms of impaired CBV in IR is crucial for developing new therapies.

Purpose of the Study:

• To investigate if inactivity alters vasoactive eicosanoid balance, contributing to microvascular IR.
• To examine the relationship between eicosanoid levels, CBV response, and IR in activity-restricted primates.

Main Methods:

• Contrast-enhanced ultrasound assessed skeletal muscle blood flow and CBV in activity-restricted (AR) and normal activity rhesus macaques.
• Plasma analysis identified vasoconstrictor hydroxyeicosatetraenoic acids (HETEs) and measured the epoxyeicosanoid (EET) to dihydroxyeicosanoid (DHET) ratio.
• Intravenous glucose tolerance tests (IVGTT) evaluated IR and glucose-stimulated CBV response.

Main Results:

• Activity-restricted primates exhibited IR and a 45% lower glucose-stimulated CBV response.
• Elevated vasoconstrictor 18-HETE and 19-HETE, along with an increased DHET/EET ratio, were observed in the AR group.
• Higher 18-HETE and 19-HETE levels correlated inversely with CBV response and directly with microvascular IR.

Conclusions:

• A shift towards increased eicosanoid vasoconstrictor tone is associated with impaired skeletal muscle vascular recruitment in IR.
• These findings suggest that altered eicosanoid balance may play a significant role in the development of microvascular IR.