The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans.
CONCLUSIONS
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.
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 A2 (TXA2 ) and prostaglandin F2α (PGF2α ), 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 TXB2 (stable TXA2 metabolite) and PGF2α , 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 TXA2 but did not change PGF2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA2 . By contrast, celecoxib decreased TXA2 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.
Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Ana
A
Cavka
Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Anita
A
Cosic
Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Ivana
I
Jukic
School of Medicine University of Zagreb, Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia.
Bojan
B
Jelakovic
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Julian H
JH
Lombard
Department of Physical Therapy, College of Applied Health Sciences, University of Illinois in Chicago, Chicago, IL, USA.
Shane A
SA
Phillips
Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia.
Vatroslav
V
Seric
Clinical Institute of Nuclear Medicine and Radiation Protection, University Hospital Osijek, Osijek, Croatia.
Ivan
I
Mihaljevic
Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Ines
I
Drenjancevic
D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D008833:Microcirculation / Q000187:drug effects*; D011188:Potassium / Q000097:blood / Q000652:urine; D011453:Prostaglandins / Q000097:blood; D012083:Renin / Q000097:blood; D012867:Skin / Q000098:blood supply; D012964:Sodium / Q000097:blood / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D013928:Thromboxane A2 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D013928:Thromboxane A2; D012964:Sodium; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D012083:Renin; D011188:Potassium