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Am J Physiol Heart Circ Physiol 288: H29-H36, 2005. First published August 26, 2004; doi:10.1152/ajpheart.00623.2004
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2004 CARDIOVASCULAR AND KIDNEY INVESTIGATORS MEETING

Chronic ANG II infusion increases NO generation by rat descending vasa recta

Zhong Zhang,1 Kristie Rhinehart,1 Glen Solis,2 Janos Pittner,1 Whaseon Lee-Kwon,1 William J. Welch,2 Christopher S. Wilcox,2 and Thomas L. Pallone1

1Division of Nephrology and Department of Physiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; and 2Division of Nephrology and Hypertension, Georgetown University, Washington, DC

Submitted 23 June 2004 ; accepted in final form 25 August 2004

We tested whether chronic ANG II infusion into rats affects descending vasa recta (DVR) contractility, synthesis of superoxide, or synthesis of nitric oxide (NO). Rats were infused with ANG II at 250 ng·kg–1·min–1 for 11–13 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 ANG II (0.1, 1, and 10 nM) was diminished, and NO generation rate was raised by chronic ANG II infusion. DHE oxidation by DVR from ANG II-infused rats was similar to controls and was significantly higher when NO synthesis was prevented with N{omega}-nitro-L-arginine methyl ester (L-NAME). The superoxide dismutase mimetic Tempol (1 mM) increased NO generation compared with controls. The increased synthesis of NO by chronic ANG II-treated vessels persisted in the presence of Tempol. DVR endothelial cytoplasmic Ca2+ response to ACh was diminished by chronic ANG II treatment, but the capacity of ACh to increase NO generation was unaltered. We conclude that DVR generation of superoxide is not affected by chronic ANG II exposure but that basal NO synthesis is increased. DVR superoxide is unlikely to be an important mediator of chronic ANG II slow pressor hypertension in rats.

medulla; kidney; microcirculation; calcium; oxidative stress


Address for reprint requests and other correspondence: T. L. Pallone, Div. of Nephrology, N3W143, 22 S. Greene St., Univ. of Maryland at Baltimore, Baltimore, MD 21201-1595 (E-mail: tpallone{at}medicine.umaryland.edu)




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