Phorbol esters elicit Ca(2+)-dependent delayed contractions in diabetic rat aorta

Area of Science:

• Vascular Physiology
• Endocrinology
• Pharmacology

Background:

• Diabetes mellitus is associated with vascular complications.
• Protein kinase C (PKC) plays a role in vascular smooth muscle contraction.
• Altered vascular responses in diabetes are not fully understood.

Purpose of the Study:

• To investigate the impact of diabetes on vascular contractility mediated by PKC activation.
• To compare the effects of phorbol esters on aortic rings from diabetic and control rats.

Main Methods:

• Aortic rings from streptozotocin-induced diabetic rats and age-matched controls were used.
• Contractions were induced by phorbol esters (phorbol 12,13-dibutyrate and 12-O-tetradecanoylphorbol 13-acetate).
• Effects of staurosporine, calcium-free medium, and nifedipine were examined.

Main Results:

• Diabetic rat aorta exhibited a delayed, sharply developing tension rise upon phorbol ester stimulation, unlike control aorta.
• Both initial and delayed contractions in diabetic aorta were abolished by staurosporine.
• The delayed phase was absent in Ca(2+)-free medium or with nifedipine, suggesting calcium channel involvement.
• Concentration-response curves showed significantly greater responses to phorbol 12,13-dibutyrate in diabetic aorta.

Conclusions:

• Diabetes enhances vascular contractile responses mediated by protein kinase C activation.
• A delayed phase of contraction, potentially involving calcium channel activation, contributes to enhanced responses in diabetic aorta.
• These findings highlight a mechanism for diabetes-induced vascular dysfunction.