Evaluation of pharmacological modulation of nitroglycerin-induced impairment of nitric oxide bioavailability by a catheter-type nitric oxide sensor.
BACKGROUND
The present study aimed to elucidate the effect of long-term treatment with nitroglycerin (NTG) on the bioavailability of nitric oxide (NO) examined by a catheter-type NO sensor. The study also examined whether these effects could be modified by an antioxidant, an angiotensin converting enzyme inhibitor, or an angiotensin II type 1 receptor antagonist (ARB).


RESULTS
Male New Zealand rabbits were treated for 7 days with NTG patches, either alone or in combination with tempol, enalapril, or valsartan (ARB). The plasma NO concentration was measured with the catheter-type NO sensor. The plasma peroxynitrite concentration was measured by enzyme-linked immunosorbent assay. An increase in plasma NO concentration in response to acetylcholine (ACh) were significantly attenuated in the NTG-treated group as compared with the control. Plasma peroxynitrite concentration in NTG-treated group was significantly higher as compared with the control. The negative effects of NTG were significantly suppressed by the co-treatment with tempol, enalapril or valsartan.


CONCLUSIONS
Chronic treatment of rabbits with NTG elicits the impairment of the ACh-stimulated NO production. In addition, the negative effects of NTG might be prevented by the co-treatment with drugs attenuating nitrosative stress.
Imanishi
Toshio
T
Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan. t-imani@wakayama-med.ac.jp
Kuroi
Akio
A
Ikejima
Hideyuki
H
Mochizuki
Seiichi
S
Goto
Masami
M
Akasaka
Takashi
T
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D005996:Nitroglycerin / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000097:blood*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D005996:Nitroglycerin