Ageing alters the production of nitric oxide and prostanoids after IL-1β 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 PGI2 levels and COX-2 expression in the three layers of the vascular wall. Ageing did not affect COX-2 expression but did increase TXA2 and PGF2α 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.