We examined whether nitroglycerin (NTG)-induced impairment of nitric oxide (NO) bioavailability could be modified by a peroxisome proliferator-activated receptor (PPAR) gammaagonist. Male New Zealand White rabbits were treated for 7 days with NTG patches, either alone or in combination with pioglitazone. Plasma NO concentration was measured with the catheter-type NO sensor located in the aorta. N(G)-methyl-L-arginine and acetylcholine (ACh) were infused into the aortic arch to measure the basal and ACh-induced plasma NO concentrations. Vascular nitrotyrosine and tetrahydrobiopterin (BH(4)) concentrations were measured by enzyme-linked immunosorbent assay and high-performance liquid chromatography with fluorescence detection, respectively. The negative effects of NTG, that is, the decrease in basal and ACh-induced NO production, were significantly suppressed by co-treatment with pioglitazone. NTG-induced increases in vascular nitrotyrosine and BH(4) concentrations were significantly decreased with co-treatment with pioglitazone. NTG-induced impairment of basal and ACh-stimulated NO production might be prevented by the co-treatment with a PPAR gamma agonist, pioglitazone through suppressions of nitrosative stress.