Ascorbic acid-induced modulation of venous tone in humans

Area of Science:

• Vascular biology
• Pharmacology
• Biochemistry

Background:

• Ascorbic acid (vitamin C) is known to possess vasodilatory properties.
• The precise mechanisms underlying ascorbic acid-induced vasodilation remain incompletely understood.

Purpose of the Study:

• To elucidate the acute effects of locally administered ascorbic acid on human veins.
• To investigate the underlying molecular mechanisms of ascorbic acid-mediated venodilation using pharmacological agents in vivo.

Main Methods:

• Ascorbic acid was infused into dorsal hand veins of healthy males, pre-constricted with phenylephrine or prostaglandin F(2alpha).
• Pharmacological inhibitors targeting nitric oxide synthase (N-monomethyl-L-arginine), cyclooxygenase (acetylsalicylic acid), cGMP generation (methylene blue), and potassium channels (quinidine, glibenclamide) were used.
• Venodilator responses were measured, and experiments were conducted in cultured bovine endothelial cells.

Main Results:

• Ascorbic acid induced dose-dependent venodilation, reversing 38% of phenylephrine-induced constriction and 51% of prostaglandin F(2alpha)-induced constriction.
• Venodilation was abolished by methylene blue (inhibiting cGMP) and quinidine (a nonselective potassium channel blocker), but not by acetylsalicylic acid or N-monomethyl-L-arginine.
• Ascorbic acid did not alter intracellular calcium in endothelial cells but blunted responses to ATP and digitonin.

Conclusions:

• Ascorbic acid dilates human veins at millimolar concentrations, likely through activation of vascular smooth muscle potassium channels mediated by cGMP.
• This vasodilatory effect is independent of endothelial nitric oxide synthase (eNOS) and cyclooxygenase products.
• The mechanism involves non-ATP-dependent potassium channels.