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

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Abstract
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.