Ageing alters the production of nitric oxide and prostanoids after IL-1beta exposure in mesenteric resistance arteries.
We aimed to analyse age influence on the production of inflammatory mediators from inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in rat mesenteric resistance arteries (MRA). The second and/or third branches of MRA from young (3-month-old) and old (22-month-old) male Sprague-Dawley rats were incubated in culture medium with or without interleukin-1ss (IL-1ss; 10 ng/ml, 14 h). IL-1ss did not modify endothelial NOS (eNOS) expression or endothelial cell distribution. However, IL-1ss increased nitrite production and iNOS expression in endothelial and smooth muscle cells more in arteries from young than from old rats. IL-1ss also increased PGI(2) levels and COX-2 expression in the three layers of the vascular wall. Ageing did not affect COX-2 expression but did increase TXA(2) and PGF(2alpha) levels. The maximum contraction to phenylephrine was increased in arteries from old rats after IL-1ss treatment. Inhibition of iNOS and COX-2 with 1400 W and NS398, respectively, abolished the differences in phenylephrine contraction. In conclusion, IL-1ss induced an inflammatory response in MRA with associated increases in iNOS and COX-2 expression. The lower increase in nitrite production from iNOS together with a greater contractile prostanoid production in the old rats would be responsible for the increase observed in their contraction to phenylephrine after IL-1 ss treatment.
Briones
Ana M
AM
Dpt. Farmacologia, Terapeutica i Toxicologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Salaices
Mercedes
M
Vila
Elisabet
E
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D051546:Cyclooxygenase 2; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007375:Interleukin-1; D011453:Prostaglandins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases