Effects of angiotensin II on NO bioavailability evaluated using a catheter-type NO sensor.
We investigated the acute or chronic effects of angiotensin (Ang) II on the bioavailability of NO in Ang II-infused rabbits using the catheter-type NO sensor. Male New Zealand White rabbits were infused with vehicle (sham), Ang II at a rate of 200 ng/kg per minute, either alone or in combination with hydralazine, Ang II type I receptor antagonist (valsartan), or an antioxidant (tempol) for 24 hours or 14 days. Plasma NO concentration was measured using the catheter-type NO sensor located in the aorta. We then infused saline (vehicle) and acetylcholine (ACh) into the aortic arch with or without pretreatment with N(G)-methyl-l-arginine. An increase in plasma NO levels in response to ACh was significantly attenuated in the Ang II group compared wit the control group. The decrease in the basal plasma NO concentration was significantly lower in the Ang II group than in the control group. Plasma peroxynitrite concentrations in Ang II group were significantly higher than in the control group. The negative effects of Ang II, that is, the decrease in basal and ACh-induced NO production and the increase in oxidative stress, were significantly suppressed by the cotreatment with either valsartan or tempol. Short-term treatment with Ang II significantly increased the ACh-induced increase in plasma NO concentration, as well as basal NO release. Although Ang II stimulates release of NO in the short term, chronic treatment with Ang II elicits the decreased NO bioavailability in the aorta of the Ang II-infusion rabbit model.
Imanishi
Toshio
T
Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan. t-imani@wakayama-med.ac.jp
Kobayashi
Katsunobu
K
Kuroi
Akio
A
Mochizuki
Seiichi
S
Goto
Masami
M
Yoshida
Kiyoshi
K
Akasaka
Takashi
T
D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002404:Catheterization / Q000295:instrumentation; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D004195:Disease Models, Animal; D006830:Hydralazine / Q000008:administration & dosage; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D016877:Oxidants / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits; D013113:Spin Labels; D013777:Tetrazoles / Q000008:administration & dosage; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D003497:Cyclic N-Oxides; D016877:Oxidants; D013113:Spin Labels; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D009569:Nitric Oxide; D000068756:Valsartan; D014633:Valine; C001803:tempol