Interleukin 1β and tumour necrosis factor α induce a macrophage‐type of nitric oxide synthase in rat renal mesangial cells

Treatment of mesangial cells with interleukin 1β (IL-1β) or tumour necrosis factor α (TNFα) has been shown to increase cGMP formation, most probably due to induction of nitric oxide synthase. Here we report that maximum stimulation of cGMP formation over a 24-h period required the presence of IL-1β or TNFα during the first 18 h of induction. N4-monomethyl-l-arginine (L-NMMA) was a potent inhibitor of cytokine-induced cGMP formation while N4-nitro-l-arginine (L-NNA) was less active. Formation of nitric oxide was detected in the cytosol of cytokine-treated mesangial cells by activation of purified soluble guanylate cyclase and was stimulated by tetrahydrobiopterin, but not by calcium calmodulin. Treatment of cells with IL-1β or TNFα markedly attenuated the contractile response to a subsequent challenge with angiotensin II. Furthermore, conditioned medium from IL-1β-treated cells increased cGMP in untreated control cells.