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The role of cyclo‐oxygenase‐1 in high‐salt diet‐induced microvascular dysfunction in humans
Author(s) -
Cavka Ana,
Cosic Anita,
Jukic Ivana,
Jelakovic Bojan,
Lombard Julian H.,
Phillips Shane A.,
Seric Vatroslav,
Mihaljevic Ivan,
Drenjancevic Ines
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp271631
Subject(s) - prostaglandin , medicine , endocrinology , thromboxane a2 , microcirculation , thromboxane , prostanoid , vasodilation , hyperaemia , endothelial dysfunction , prostacyclin , prostaglandin h2 , endothelium , reactive hyperemia , cyclooxygenase , blood flow , chemistry , blood pressure , biochemistry , platelet , enzyme
Key points Recent studies have shown that some of the deleterious effects of a high‐salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function. Increased generation of cyclo‐oxygenase (COX‐1 and COX‐2)‐derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading. The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX‐1 and COX‐2 in normotensive subjects on a short‐term HS diet. The present study demonstrates the important role of COX‐1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet. These results help to explain how even short‐term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX‐1 could play a role in this impaired tissue blood flow.Abstract The present study aimed to assess the effect of a 1‐week high‐salt (HS) diet on the role of cyclo‐oxygenases (COX‐1 and COX‐2) and the vasoconstrictor prostaglandins, thromboxane A 2 (TXA 2 ) and prostaglandin F 2α (PGF 2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women ( n = 54) were assigned to either the HS diet group ( N = 30) (∼14 g day –1 NaCl ) or low‐salt (LS) diet group ( N = 24) (<2.3 g day –1 NaCl ) for 7 days. Post‐occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB 2 (stable TXA 2 metabolite) and PGF 2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non‐selective COX‐1 and COX‐2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX‐2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty‐four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA 2 but did not change PGF 2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA 2 . By contrast, celecoxib decreased TXA 2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX‐1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.