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Am J Physiol Heart Circ Physiol (August 26, 2004). doi:10.1152/ajpheart.00623.2004
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Submitted on June 23, 2004
Accepted on August 25, 2004

Chronic AngII Infusion Increases NO Generation by Rat Descending Vasa Recta

Zhong Zhang, Kristie Rhinehart, Glen Solis, Janos Pittner, Whaseon Lee-Kwon, William J Welch, Christopher S Wilcox, and Thomas L Pallone*

* To whom correspondence should be addressed. E-mail: tpallone{at}medicine.umaryland.edu.

We tested whether chronic angiotensin II infusion into rats affects descending vasa recta (DVR) contractility, synthesis of superoxide or synthesis of nitric oxide (NO). Rats were infused with AngII at 250 ng Kg-1 min-1 for 11 to 13 days. DVR were loaded with dihydroethidium (DHE) to measure superoxide and 3-amino, 4-aminomethyl-2',7'-difluorofluorescein (DAFFM) to measure NO. Acute constriction of DVR by AngII (0.1, 1, 10 nM) was diminished and NO generation rate was raised by chronic AngII infusion. DHE oxidation by DVR from AngII infused rats was similar to controls and was significantly higher when NO synthesis was prevented with n{omega}-nitro-L-arginine methyl ester (LNAME). The superoxide dismutase mimetic, tempol (1 mM) increased NO generation compared to controls. The increased synthesis of NO by chronic AngII treated vessels persisted in the presence of tempol. DVR endothelial cytoplasmic Ca2+ response to acetylcholine (ACh) was diminished by chronic AngII treatment but the capacity of ACh to increase NO generation was unaltered. We conclude that DVR generation of superoxide is not affected by chronic AngII exposure but that basal NO synthesis is increased. DVR superoxide superoxide is unlikely to be an important mediator of chronic AngII slow pressor hypertension in rats.




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