Effects of the chronic in vivo administration of L-NAME on the contractileresponses of the rat perfused mesenteric bed

1 The effects of the chronic in vivo inhibition of nitric oxide synthase (N OS) with N-omega-nitro-L-arginine methyl ester (L-NAME) on vascular contrac tility were studied in the rat perfused mesenteric bed. The chronic treatme nt with L-NAME during 4 weeks induced a rise in systolic blood pressure (ba sal: 115.1 +/- 6.5 mmHg; chronic L-NAME-treatment: 171.7 +/- 7.7 mmHg, n = 16, P < 0.05). 2 After the chronic NOS inhibition, the potentiation of the maximal vasocon strictor responses to noradrenaline, phenylephrine and KCl was to the same extent as that observed after the in vitro exposure to 100 mu M L-NAME. 3 No further potentiation of the contractile responses was achieved when th e mesenteric beds isolated from L-NAME treated rats were-incubated in vitro with 100 mu M L-NAME. 4 The endothelium removal but not the inhibition of prostanoid synthesis wi th either 10 mu M indomethacin or 10 mu M 17-octadecynoic acid potentiated the contractions to noradrenaline and to KCl both under control conditions as well as after the chronic in vivo administration of L-NAME. 5 These observations taken together suggest that:after chronic L-NAME maxim um inhibition of nitric oxide synthase was achieved and no compensatory mec hanisms able to counterbalance the increase in contractile responses were d eveloped. 6 Further studies are necessary to elucidate the nature of the factors, oth er than nitric oxide, that contribute to the potentiation of contractile re sponses observed when the endothelium is removed after L-NAME treatment.