Hypertension, Vol 20, 298-303, Copyright © 1992 by American Heart Association
MO Ribeiro, E Antunes, G de Nucci, SM Lovisolo and R Zatz
Recent studies have indicated that acute inhibition of nitric oxide
biosynthesis in the rat promotes arterial hypertension and renal
vasoconstriction. We evaluated the renal and systemic effects of 4-6 weeks
of nitric oxide blockade in Munich-Wistar rats receiving the nitric oxide
inhibitor nitro-L-arginine orally. Age-matched untreated rats were used as
controls. In an additional seven rats, nitric oxide blockade was carried
out in conjunction with oral administration of the novel angiotensin II
antagonist losartan potassium. Tail-cuff pressure rose progressively in
nitro-L-arginine-treated rats, reaching 164 +/- 6 mm Hg at 4-6 weeks,
compared with 108 +/- 3 mm Hg in controls. In rats concomitantly receiving
losartan, tail-cuff pressure reached 125 +/- 6 mm Hg, still elevated
compared with rats receiving losartan alone (98 +/- 3 mm Hg).
Nitro-L-arginine-treated rats presented marked renal vasoconstriction and
hypoperfusion, as well as a 30% fall in glomerular filtration rate and a
39% increase in filtration fraction. Treatment with Losartan normalized
glomerular filtration rate, but not filtration fraction or renal vascular
resistance. Plasma renin activity was elevated after nitro-L-arginine
treatment. Renal histological examination revealed widespread arteriolar
narrowing, focal arteriolar obliteration, and segmental fibrinoid necrosis
in the glomeruli. In a separate group of rats, nitro-L-arginine
administered for 1 week induced hypertension that was partially reversed by
acute L-arginine, but not D-arginine or L-glycine, infusions. We conclude
that chronic nitric oxide blockade may constitute a new model of severe
arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension
Department of Internal Medicine, University of Sao Paulo School of Medicine, Brazil.
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 Y. Ohmachi, W. Toriumi, K. Takashima, and K. Doi Systemic Histopathology of Rats Treated with 6-Sulfanilamidoindazole, a Novel Arthritogenic Sulfonamide Toxicol Pathol, March 1, 1998; 26(2): 262 - 270. [Abstract] [PDF]
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C. K. Fujihara, D. M. A. C. Malheiros, J. L. Donato, A. Poli, G. De Nucci, and R. Zatz Nitroflurbiprofen, a new nonsteroidal anti-inflammatory, ameliorates structural injury in the remnant kidney Am J Physiol Renal Physiol, March 1, 1998; 274(3): F573 - F579. [Abstract] [Full Text] [PDF]
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A. Godecke, U. K. M. Decking, Z. Ding, J. Hirchenhain, H.-J. Bidmon, S. Godecke, and J. Schrader Coronary Hemodynamics in Endothelial NO Synthase Knockout Mice Circ. Res., February 9, 1998; 82(2): 186 - 194. [Abstract] [Full Text] [PDF]
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C. Qiu, D. Muchant, W. H. Beierwaltes, L. Racusen, and C. Baylis Evolution of Chronic Nitric Oxide Inhibition Hypertension: Relationship to Renal Function Hypertension, January 1, 1998; 31(1): 21 - 26. [Abstract] [Full Text]
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M. Takemoto, K. Egashira, H. Tomita, M. Usui, H. Okamoto, A. Kitabatake, H. Shimokawa, K. Sueishi, and A. Takeshita Chronic Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade : Effects on Cardiovascular Remodeling in Rats Induced by the Long-term Blockade of Nitric Oxide Synthesis Hypertension, December 1, 1997; 30(6): 1621 - 1627. [Abstract] [Full Text]
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J.-M. Chillon, S. Ghoneim, and G. L. Baumbach Effects of Chronic Nitric Oxide Synthase Inhibition on Cerebral Arterioles in Rats Hypertension, November 1, 1997; 30(5): 1097 - 1104. [Abstract] [Full Text]
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L. I. Juncos, J. C. Cornejo, J. Gomes, S. Baigorria, and L. A. Juncos Abnormal Endothelium-Dependent Responses in Early Radiation Nephropathy Hypertension, September 1, 1997; 30(3): 672 - 676. [Abstract] [Full Text]
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M. Sander, J. Hansen, and R. G. Victor The Sympathetic Nervous System Is Involved in the Maintenance but Not Initiation of the Hypertension Induced by N{omega}-Nitro-L-Arginine Methyl Ester Hypertension, July 1, 1997; 30(1): 64 - 70. [Abstract] [Full Text]
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P. Sventek, A. Turgeon, and E. L. Schiffrin Vascular Endothelin-1 Gene Expression and Effect on Blood Pressure of Chronic ETA Endothelin Receptor Antagonism After Nitric Oxide Synthase Inhibition With L-NAME in Normal Rats Circulation, January 7, 1997; 95(1): 240 - 244. [Abstract] [Full Text]
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 E. G. Shesely, N. Maeda, H.-S. Kim, K. M. Desai, J. H. Krege, V. E. Laubach, P. A. Sherman, W. C. Sessa, and O. Smithies Elevated blood pressures in mice lacking endothelial nitric oxide synthase PNAS, November 12, 1996; 93(23): 13176 - 13181. [Abstract] [Full Text] [PDF]
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P. R. Knoblich, R. H. Freeman, and D. Villarreal Pressure-Dependent Renin Release During Chronic Blockade of Nitric Oxide Synthase Hypertension, November 1, 1996; 28(5): 738 - 742. [Abstract] [Full Text]
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Y. Erlich and T. Rosenthal Contribution of Nitric Oxide to the Beneficial Effects of Enalapril in the Fructose-Induced Hyperinsulinemic Rat Hypertension, November 1, 1996; 28(5): 754 - 757. [Abstract] [Full Text]
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D. Henrion, F. J. Dowell, B. I. Levy, and J.-B. Michel In Vitro Alteration of Aortic Vascular Reactivity in Hypertension Induced by Chronic NG-Nitro-L-Arginine Methyl Ester Hypertension, September 1, 1996; 28(3): 361 - 366. [Abstract] [Full Text]
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M. E. Ullian, D. J. Hazen-Martin, L. G. Walsh, R. K. Davda, and B. M. Egan Carbenoxolone Damages Endothelium and Enhances Vasoconstrictor Action in Aortic Rings Hypertension, June 1, 1996; 27(6): 1346 - 1352. [Abstract] [Full Text]
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S. S. Yamada, A. L. Sassaki, C. K. Fujihara, D. M. Avancini Costa Malheiros, G. De Nucci, and R. Zatz Effect of Salt Intake and Inhibitor Dose on Arterial Hypertension and Renal Injury Induced by Chronic Nitric Oxide Blockade Hypertension, May 1, 1996; 27(5): 1165 - 1172. [Abstract] [Full Text]
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N. Bouriquet, M. Dupont, A. Herizi, A. Mimran, and D. Casellas Preglomerular Sudanophilia in L-NAME Hypertensive Rats : Involvement of Endothelin Hypertension, March 1, 1996; 27(3): 382 - 391. [Abstract] [Full Text]
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H. Ono, Y. Ono, and E. D. Frohlich ACE Inhibition Prevents and Reverses L-NAMEExacerbated Nephrosclerosis in Spontaneously Hypertensive Rats Hypertension, February 1, 1996; 27(2): 176 - 183. [Abstract] [Full Text]
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H. Guan, V. Cachofeiro, M. L. Pucci, P. M. Kaminski, M. S. Wolin, and A. Nasjletti Nitric Oxide and the Depressor Response to Angiotensin Blockade in Hypertension Hypertension, January 1, 1996; 27(1): 19 - 24. [Abstract] [Full Text]
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H. Takase, P. Moreau, C. F. Kung, E. Nava, and T. F. Luscher Antihypertensive Therapy Prevents Endothelial Dysfunction in Chronic Nitric Oxide Deficiency : Effect of Verapamil and Trandolapril Hypertension, January 1, 1996; 27(1): 25 - 31. [Abstract] [Full Text]
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S. Grunfeld, C. A. Hamilton, S. Mesaros, S. W. McClain, A. F. Dominiczak, D. F. Bohr, and T. Malinski Role of Superoxide in the Depressed Nitric Oxide Production by the Endothelium of Genetically Hypertensive Rats Hypertension, December 1, 1995; 26(6): 854 - 857. [Abstract] [Full Text]
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K. Numaguchi, K. Egashira, M. Takemoto, T. Kadokami, H. Shimokawa, K. Sueishi, and A. Takeshita Chronic Inhibition of Nitric Oxide Synthesis Causes Coronary Microvascular Remodeling in Rats Hypertension, December 1, 1995; 26(6): 957 - 962. [Abstract] [Full Text]
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R. A. Cohen and P. M. Vanhoutte Endothelium-Dependent Hyperpolarization : Beyond Nitric Oxide and Cyclic GMP Circulation, December 1, 1995; 92(11): 3337 - 3349. [Full Text]
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 P. Moreau, H. Takase, C. F. Kung, M.-M. van Rooijen, T. Schaffner, and T. F. Luscher Structure and Function of the Rat Basilar Artery During Chronic Nitric Oxide Synthase Inhibition Stroke, October 1, 1995; 26(10): 1922 - 1929. [Abstract] [Full Text]
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E. Delacretaz, A. Zanchi, J. Nussberger, D. Hayoz, J.-F. Aubert, H. R. Brunner, and B. Waeber Chronic Nitric Oxide Synthase Inhibition and Carotid Artery Distensibility in Renal Hypertensive Rats Hypertension, August 1, 1995; 26(2): 332 - 336. [Abstract] [Full Text]
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M. O. Ribeiro, E. Antunes, M. N. Muscara, G. De Nucci, and R. Zatz Nifedipine Prevents Renal Injury in Rats With Chronic Nitric Oxide Inhibition Hypertension, July 1, 1995; 26(1): 150 - 155. [Abstract] [Full Text]
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A. W. Cowley Jr, D. L. Mattson, S. Lu, and R. J. Roman The Renal Medulla and Hypertension Hypertension, April 1, 1995; 25(4): 663 - 673. [Abstract] [Full Text]
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H. Nakamoto, C. M. Ferrario, S. B. Fuller, D. L. Robaczewski, E. Winicov, and R. H. Dean Angiotensin-(1-7) and Nitric Oxide Interaction in Renovascular Hypertension Hypertension, April 1, 1995; 25(4): 796 - 802. [Abstract] [Full Text]
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C. Qiu, K. Engels, L. Samsell, and C. Baylis Renal Effects of Acute Amino Acid Infusion in Hypertension Induced by Chronic Nitric Oxide Blockade Hypertension, January 1, 1995; 25(1): 61 - 66. [Abstract] [Full Text]
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 T. J. Spyt, K. L. Blake, P. A. C. Watt, and H. Thurston Inhibition of Endothelium-Dependent Relaxation by Free Hemoglobin in the Human Internal Thoracic Artery Vascular and Endovascular Surgery, January 1, 1994; 28(1): 1 - 6. [Abstract] [PDF]
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