Chronic ANG II infusion increases NO generation by rat descending vasa recta.
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 Ca(2+) 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.
Zhang
Zhong
Z
Division of Nephrology, Department of Physiology, University of MarylandSchool of Medicine, Baltimore, MD, USA.
Rhinehart
Kristie
K
Solis
Glen
G
Pittner
Janos
J
Lee-Kwon
Whaseon
W
Welch
William J
WJ
Wilcox
Christopher S
CS
Pallone
Thomas L
TL
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001682:Biological Availability; D020013:Calcium Signaling / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004996:Ethidium / Q000031:analogs & derivatives* / Q000378:metabolism; D007260:Infusion Pumps; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067883:dihydroethidium; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D004996:Ethidium; D000109:Acetylcholine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester