Effect of pioglitazone on nitroglycerin-induced impairment of nitric oxide bioavailability by a catheter-type nitric oxide sensor.
BACKGROUND
We examined whether nitroglycerin (NTG)-induced impairment of nitric oxide (NO) bioavailability could be modified by a peroxisome proliferator-activated receptor (PPAR) gammaagonist.


RESULTS
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.


CONCLUSIONS
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.
Ikejima
Hideyuki
H
Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
Imanishi
Toshio
T
Tsujioka
Hiroto
H
Kuroi
Akio
A
Muragaki
Yasuteru
Y
Mochizuki
Seiichi
S
Goto
Masami
M
Yoshida
Kiyoshi
K
Akasaka
Takashi
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002138:Calibration; D002404:Catheterization / Q000295:instrumentation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000295:instrumentation* / Q000379:methods; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000097:blood*; D005996:Nitroglycerin / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D011817:Rabbits; D045162:Thiazolidinediones / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D001708:Biopterins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C003402:sapropterin; D005996:Nitroglycerin; D000109:Acetylcholine; D000077205:Pioglitazone