Protection of endothelial-derived vasorelaxation with cariporide, a sodium-proton exchanger inhibitor, after prolonged hypoxia and hypoxia-reoxygenation: effect of age.
Calcium overload during hypoxia and reoxygenation exerts deleterious effects in endothelial and smooth muscle cells but potential effects of sodium-proton exchanger (NHE) inhibitors have never been investigated in both adult and senescent vessels. Isolated aortic rings from adult and senescent rats were submitted to hypoxia (50 min) or to hypoxia/reoxygenation (20/30 min) without or with cariporide (10(-6) M) and aortic vasoreactivity was recorded. After hypoxia, relaxation to acetylcholine was preserved in adult rings treated with cariporide (-22.3% vs. -9.3% of baseline value in control and treated groups respectively, P<0.05) but not in senescents. Cariporide treatment restored relaxation to acetylcholine after hypoxia-reoxygenation in adult rings (-32.04% vs. -0.03% of baseline value in control and treated groups respectively, P<0.01) and to a lesser extent, in senescent rings (-30.8% vs. -24.4% of baseline value in control and treated groups respectively, P<0.01). These results suggested that hypoxia induced lower acidosis and/or involved other mechanisms of proton extrusion than NHE in senescent aorta. Improvement of endothelial function with cariporide after reoxygenation in senescent aorta, but in a lesser extent than in adult aorta, suggests a lower role of NHE in pH regulation and subsequent calcium overload during aging.
Besse
Sophie
S
Laboratoire Croissance cellulaire, Réparation et Régénération Tissulaires, UMR CNRS 7149, Université Paris 12-Val de Marne, Créteil, France. Sophie.Besse@univ-paris5.fr
Tanguy
Stéphane
S
Boucher
François
F
Huraux
Catherine
C
Riou
Bruno
B
Swynghedauw
Bernard
B
de Leiris
Joël
J
D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; C093373:cariporide; D000109:Acetylcholine; D010100:Oxygen