The role of cyclooxygenase-1 in high salt diet-induced microvascular dysfunction in humans

Abstract

Objectives

To assess the effect of 1-week high salt (HS) diet on the role of cyclooxygenases (COX-1,-2) and vasoconstrictor prostaglandins - thromboxane A₂ (TXA₂) and prostaglandin F2α (PGF_2α) on skin microcirculatory blood flow and to detect its effect on markers of endothelial activation such a soluble cell adhesion molecules (sCAMs).

Methods

Young women (N = 54) were assigned to either HS diet group (N = 30) (_∼14 g of NaCl/day) or low salt (LS) diet group (N = 24) (<2.3 g NaCl/day) for 7 days. Post-occlusive reactive hyperemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry (LDF). Plasma Renin Activity (PRA), plasma aldosterone, plasma and 24 h-urine sodium and potassium, plasma concentrations of TXB₂ (stable TXA₂ metabolite) and PGF_2α, sCAMs and blood pressure (BP) were measured before and after diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1,2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating LDF measurements.

Results

BP was unchanged after HS diet, but significantly reduced after LS diet. 24 h-urinary sodium was increased, PRA and plasma aldosterone levels decreased after HS diet. HS diet significantly impaired PORH and increased TXA₂, but did not change PGF_2α levels. Indomethacin restored microcirculatory blood flow, reduced TXA₂. In contrast, celecoxib decreased TXA₂ levels, but had no significant effects on blood flow.

Conclusions

Restoration of of PORH by indomethacin during high salt diet suggest an important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during high salt intake.

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