In the rabbit renal afferent arteriole aldosterone counteracts depolarization [high K ⁺]-induced contractions in a nitric oxide (NO) dependent way. The effect is rapid, transient, and is prolonged after inhibition of gene transcription with actinomycin D. The objective of the present study was to investigate the genomic effect of aldosterone that attenuates dilatation in small resistance vessels. Isolated mesenteric arterioles (diameter:60 to 140 micron) from mice were mounted with a set of glass pipettes, perfused (inflow pressure 60 mmHg, outflow 55 mmHg) and placed in an organ chamber containing physiological salt solution (PSS) at 37 °C with continuous superfusion. During stimulation with physiological salt solution containing 70 mM K⁺ the vessels contracted (inner diameter reduced to ~25% of control) and after 60 seconds of stimulation dilated to ~60% of control diameter (recovery). Pre-treatment of the arterioles with aldosterone (1nM, 50 min) inhibited the recovery significantly. After inhibition of gene transcription with actinomycin D (1 mM), aldosterone had no effect on recovery. The non-selective COX inhibitor, indomethacin blocked the effect of aldosterone whereas the COX-2 selective antagonist NS-398 and S18886 (TP receptor antagonist) had no significant effect. Arterioles from endothelial nitric oxide synthase (eNOS) knockout mice exhibited a significantly attenuated recovery. Dilatation in these vessels in response to the NO- donor sodium nitroprusside (100 nM) was inhibited by aldosterone (1nM, 50 min). In conclusion, long term aldosterone exposure attenuates NO-dependent recovery after depolarization in small mesenteric resistance vessels from the mouse through a genomic effect that involves COX-1 activity. This mechanism could participate to the detrimental effects of aldosterone on the vasculature.