engleski

Cyclooxygenase-1, not cyclooxygenase-2 derived prostaglandins alters microvascular reactivity during high salt loading in young healthy humans

Our recent study demonstrated that one week of high salt diet (HSD) impaired skin microcirculatory hyperemic blood flow, which was restored with indomethacin – nonselective inhibitor of cyclooxygenase-1 and -2 (COX-1, COX- 2). The aim of this study was to determine which COX isoform and its derived prostaglandins are involved in altered microvascular reactivity during HSD. Skin microvascular post occlusive hyperemic blood flow was assessed by laser Doppler flowmetry (LDF) before and after 7 days HSD protocol (intake more than 240 mmol Na/day) in 15 healthy female subjects. One group received 100mg of indomethacin 90 minutes, and another group 200mg of celecoxib 180 minutes before repeated LDF measurements. Plasma concentration of stable TXA2 metabolite [TXB2] was measured before and after HSD. Plasma Renin Activity (PRA), plasma aldosterone and both plasma and 24h urine sodium, potassium, urea and creatinine levels were measured before and after HSD protocol. Blood pressure and heart rate (HR) were measured at the beginning of each LDF assessment. No significant changes in BP or HR occurred during the study. Increased urinary sodium and decreased PRA and plasma aldosterone levels confirmed subjects conformed to the diet guidelines. As previously reported, HSD caused significant impairment in post occlusion hyperemic blood flow. Indometacin administration before HSD significantly reduced, while its administration after HSD restored post occlusion blood flow to control values. Plasma [TXB2] was increased after HSD. Indomethacin significantly decreased plasma [TXB2] before and after HSD, celecoxib administration didn’t induce significant changes in post occlusion blood flow or [TXB2] both, before and after HSD protocol. The present study confirmed that indomethacin restored impaired post occlusion microvascular blood flow after one week of HSD. Increased plasma level of vasoconstrictor metabolite [TXB2] seems to be mediated dominantly by COX-1, not COX-2. These results suggest that COX-1 but not COX-2 derived prostaglandins, both vasodilator and vasoconstrictor, play significant role in regulation of microvascular blood flow in young healthy humans.

laser doppler flowmetry; high salt diet; cyclooxigenases; vascular function

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