Prazosin Can Prevent Glucocorticoid Mediated Capillary Rarefaction

Area of Science:

• Physiology
• Molecular Biology
• Endocrinology

Background:

• Glucocorticoids (GC) induce skeletal muscle capillary rarefaction, impairing muscle function.
• The underlying mechanisms of GC-induced capillary rarefaction are not fully understood.
• Alpha-1 adrenergic receptor inhibition with prazosin promotes angiogenesis in healthy skeletal muscle.

Purpose of the Study:

• To investigate the mechanisms of GC-induced skeletal muscle capillary rarefaction.
• To determine if prazosin can reverse GC-induced capillary loss and promote angiogenesis.
• To examine the effects of corticosterone (CORT) and prazosin on specific molecular signaling pathways.

Main Methods:

• Male Sprague Dawley rats received corticosterone (CORT) pellets with or without prazosin treatment for 1-2 weeks.
• Skeletal muscle capillary-to-fiber ratio (C:F) was assessed.
• mRNA and protein levels of Angiopoietin-1 (Ang-1), VEGF-A, TGFβ1, and MMP-2 were measured.
• Cultured skeletal muscle endothelial cells were used to assess shear stress signaling.

Main Results:

• CORT treatment for 2 weeks significantly reduced the C:F ratio, indicating capillary rarefaction.
• Concurrent prazosin administration prevented CORT-induced capillary rarefaction.
• CORT reduced Ang-1 mRNA levels, which was partially restored by prazosin.
• Prazosin increased VEGF-A mRNA and protein in CORT-treated rats.
• CORT blunted shear stress-induced Akt phosphorylation in endothelial cells.

Conclusions:

• GC-mediated capillary rarefaction in skeletal muscle is linked to reduced Ang-1 mRNA.
• Prazosin treatment prevents GC-induced capillary loss by upregulating VEGF-A.
• Prazosin does not induce angiogenesis in GC-treated muscle, unlike in healthy muscle.