Ageing affects nitric oxide synthase, cyclooxygenase and oxidative stress enzymes expression differently in mesenteric resistance arteries.
1 Our aim was to study the role of nitric oxide (NO) and arachidonic acid pathways in the alpha(1)-adrenoceptor-mediated vasoconstriction in mesenteric resistance arteries from 3--4 and 22 to 23-month-old Sprague-Dawley rats. 2 The expression of NO synthase (NOS), cyclooxygenase (COX) isoforms, soluble guanylate cyclase, superoxide dismutase and the NAD(P)H oxidase subunits p22(phox) and p 47(phox) were determined. 3 The N(G)-nitro-l-arginine methyl ester, a non-selective NOS inhibitor, shifted to the left but indomethacin and NS 398, non-selective and selective COX-2 inhibitors, shifted to the right the concentration-response curve for the vasoconstriction by phenylephrine in both age groups. 4 Ageing up-regulated endothelial NOS and p22(phox) expression but did not modify COX, soluble guanylate cyclase, superoxide dismutase and p 47(phox) expression. 5 These data suggest that the observed enhancement of eNOS protein expression could constitute a compensatory mechanism to counter-regulate a chronic loss of NO possibly through increased superoxide anion production from NAD(P)H oxidase induced by age.
Briones
A M
AM
Departament de Farmacologia, de Terapèutica i de Toxicologia, Facultat de Medicine, Institute de Neuroxiencies, Universitat Automona de Barcelona, 08193 Bellaterra, Spain.
Montoya
N
N
Giraldo
J
J
Vila
E
E
D000109:Acetylcholine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D018384:Oxidative Stress; D010656:Phenylephrine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010656:Phenylephrine; D019255:NADPH Oxidases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin