Facilitation of renal autoregulation by angiotensin II is mediated through modulation of nitric oxide

• Published in: Acta physiologica Scandinavica Vol. 179; no. 2; pp. 189 - 201
• Main Authors: Guan, Z., Willgoss, D. A., Matthias, A., Manley, S. W., Crozier, S., Gobe, G., Endre, Z. H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.2003; Blackwell Science
• Subjects: angiotensin II; Angiotensin II - physiology; Angiotensin Receptor Antagonists; Animals; Biological and medical sciences; Cyclic N-Oxides - pharmacology; endothelium derived hyperpolarizing factor; Endothelium-Dependent Relaxing Factors - metabolism; erythrocyte perfused rat kidney; Erythrocytes - physiology; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate; Homeostasis - physiology; Indomethacin - pharmacology; isolated perfused rat kidney; Kidney - drug effects; Kidney - physiology; Losartan - pharmacology; Male; myogenic response; NG-Nitroarginine Methyl Ester - metabolism; nitric oxide; Nitric Oxide - physiology; Nitric Oxide Synthase - metabolism; Perfusion; phenylephrine; Phenylephrine - metabolism; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Sprague-Dawley; renal autoregulation; Spin Labels; tubuloglomerular feedback; Vasoconstriction - physiology; Vertebrates: urinary system; Prostaglandin-endoperoxide synthase; Peptides; Rat; renal autoregulation; Kidney; Vasomotricity; erythrocyte perfused rat kidney; Eicosanoid; phenylephrine; Mechanism of action; Angiotensin II; tubuloglomerular feedback; myogenic response; Prostaglandin; Enzyme; Arachidonic acid derivatives; Rodentia; Vasoconstriction; AT1 angiotensin receptor; isolated perfused rat kidney; Nitric-oxide synthase; endothelium derived hyperpolarizing factor; Renin angiotensin system; Vertebrata; Hyperoxides; Mammalia; Urinary system; Nitric oxide; Self regulation; Oxidoreductases
• ISSN: 0001-6772; 1365-201X
• DOI: 10.1046/j.1365-201X.2003.01125.x

Aims: This study was designed to investigate the influence of angiotensin II (Ang II) and nitric oxide (NO) on autoregulation of renal perfusion. Methods: Autoregulation was investigated in isolated perfused kidneys (IPRK) from Sprague‐Dawley rats during stepped increases in perfusion pressure. Results: Ang II (75–200 pM) produced dose‐dependent enhancement of autoregulation whereas phenylephrine produced no enhancement and impaired autoregulation of GFR. Enhancement by Ang II was inhibited by the AT1 antagonist, Losartan, and the superoxide scavenger, Tempol. Under control conditions nitric oxide synthase (NOS) inhibition by 10 μm N‐omega‐nitro‐ιl‐arginine methyl ester (ιl‐NAME) facilitated autoregulation in the presence of non‐specific cyclooxygenase (COX) inhibition by 10 μm indomethacin. Both COX and combined NOS/COX inhibition reduced the autoregulatory threshold concentration of Ang II. Facilitation by 100 pm Ang II was inhibited by 100 μm frusemide. Methacholine (50 nm) antagonised Ang II‐facilitated autoregulation in the presence and absence of NOS/COX inhibition. Infusion of the NO donor, 1 μm sodium nitroprusside, inhibited ιl‐NAME enhancement of autoregulation under control conditions and during Ang II infusion. Conclusions: The results suggest than an excess of NO impairs autoregulation under control conditions in the IPRK and that endogenous and exogenous NO, vasodilatory prostaglandins and endothelium‐derived hyperpolarizing factor (EDHF) activity antagonise Ang II‐facilitated autoregulation. Ang II also produced a counterregulatory vasodilatory response that included prostaglandin and NO release. We suggest that Ang II facilitates autoregulation by a tubuloglomerular feedback–dependent mechanism through AT1 receptor‐mediated depletion of nitric oxide, probably by stimulating generation of superoxide.