What Can Current Stimulation Tell Us about the Vascular Function of Endogenous Prostacyclin in Healthy Rat Skin In Vivo?

Abstract

In endothelial function, prostacyclin (PGI(2)) is as important as nitric oxide (NO); however, no test assesses specifically the vascular function of endogenous PGI(2). We hypothesized that PGI(2) has a dominant role in cathodal current-induced vasodilation (CIV) described in human skin. We thus aimed to study, in physiological conditions, the PGI(2) involvement in cathodal CIV in rats in order to use pharmacological blockers that could not be used in humans. CIV was reduced by cyclooxygenase (COX)-1 and PGI(2) synthase (PGIS) and PGI(2) receptor (IP) blockers, but was unchanged by COX-2 and NO synthase (NOS) blockers. The level of 6-ketoPGF(1)(α) present in skin biopsies, measured as endogenous PGI(2), was increased by cathodal current stimulation, except under COX-1 and PGIS inhibition. This study provides evidence that cathodal CIV mainly relies on the release of PGI(2) endogenously produced through the COX-1/PGIS pathway, and then acts on IP receptors to relax the cutaneous microvessels in healthy rats. In contrast, neither COX-2 nor NOS is involved in CIV and the endogenous PGI(2) release by current stimulation. This finding shows that cathodal current stimulation could be a valuable method to assess the vascular function of endogenous PGI(2) in healthy skin.