This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henrion, D. Articles by Michel, J.-B. Search for Related Content PubMed PubMed Citation Articles by Henrion, D. Articles by Michel, J.-B.

(Hypertension. 1996;28:361-366.)
© 1996 American Heart Association, Inc.

Articles

In Vitro Alteration of Aortic Vascular Reactivity in Hypertension Induced by Chronic N^G-Nitro-L-Arginine Methyl Ester

Daniel Henrion; Fiona J. Dowell; Bernard I. Levy; Jean-Baptiste Michel

Institut National de la Sante et de la Recherche Medicale (INSERM) U141, IFR Circulation–Lariboisiere, Universite Paris VII, Hopital Lariboisiere, and INSERM U367 (J.-B.M.), Paris, France.

Correspondence to D. Henrion, PhD, INSERM U141, Hopital Lariboisiere, 41 Bd de la Chapelle, 75475 Paris, Cedex 10, France.

Chronic administration of N^G-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I–converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME–induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME–treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside–induced dilation was increased in both L-NAME– and L-NAME plus quinapril–treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K⁺ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF₄^-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside–induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF₄^-, K⁺, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530±120 fmol/mg protein, n=12, P<.05) and L-NAME plus quinapril (461±140 fmol/mg protein, n=12, P<.05) compared with controls (1798±522 fmol/mg protein, n=12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME–treated rats.

Key Words: aorta • blood vessels • rats • nitric oxide • angiotensin II • phenylephrine • angiotensin-converting enzyme inhibitors

This article has been cited by other articles:

				D. Chansel, M. Ciroldi, S. Vandermeersch, L. F Jackson, A.-M. Gomez, D. Henrion, D. C. Lee, T. M. Coffman, S. Richard, J.-C. Dussaule, et al. Heparin binding EGF is necessary for vasospastic response to endothelin FASEB J, September 1, 2006; 20(11): 1936 - 1938. [Abstract] [Full Text] [PDF]

				I. F. Benter, M. H. M. Yousif, J. T. Anim, C. Cojocel, and D. I. Diz Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H684 - H691. [Abstract] [Full Text] [PDF]

				G. Rossoni, B. Manfredi, P. Del Soldato, and F. Berti The Nitric Oxide-Releasing Naproxen Derivative Displays Cardioprotection in Perfused Rabbit Heart Submitted to Ischemia-Reperfusion J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 555 - 562. [Abstract] [Full Text] [PDF]

				M.-C. Bouton, B. Richard, P. Rossignol, M. Philippe, M.-C. Guillin, J.-B. Michel, and M. Jandrot-Perrus The Serpin Protease-Nexin 1 Is Present in Rat Aortic Smooth Muscle Cells and Is Upregulated in L-NAME Hypertensive Rats Arterioscler Thromb Vasc Biol, January 13, 2003; 23(1): 142 - 147. [Abstract] [Full Text] [PDF]

				P. Jolma, J. Kalliovalkama, J.-P. Tolvanen, P. Koobi, M. Kahonen, N. Hutri-Kahonen, X. Wu, and I. Porsti High-calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1036 - H1043. [Abstract] [Full Text] [PDF]

				M. N. Muscara, W. McKnight, F. Lovren, C. R. Triggle, G. Cirino, and J. L. Wallace Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H528 - H535. [Abstract] [Full Text] [PDF]

				W. Gonzalez, V. Fontaine, M. E. Pueyo, N. Laquay, D. Messika-Zeitoun, M. Philippe, J.-F. Arnal, M.-P. Jacob, and J.-B. Michel Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension : Modulation of Proinflammatory Signals Hypertension, July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF]

				A. B. Driss, C. Devaux, D. Henrion, M. Duriez, C. Thuillez, B. I. Levy, and J.-B. Michel Hemodynamic Stresses Induce Endothelial Dysfunction and Remodeling of Pulmonary Artery in Experimental Compensated Heart Failure Circulation, June 13, 2000; 101(23): 2764 - 2770. [Abstract] [Full Text] [PDF]

				J. Kalliovalkama, P. Jolma, J.-P. Tolvanen, M. Kahonen, N. Hutri-Kahonen, X. Wu, P. Holm, and I. Porsti Arterial function in nitric oxide-deficient hypertension: influence of long-term angiotensin II receptor antagonism Cardiovasc Res, June 1, 1999; 42(3): 773 - 782. [Abstract] [Full Text] [PDF]

				G. Luvara, M. E. Pueyo, M. Philippe, C. Mandet, F. Savoie, D. Henrion, and J.-B. Michel Chronic Blockade of NO Synthase Activity Induces a Proinflammatory Phenotype in the Arterial Wall : Prevention by Angiotensin II Antagonism Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1408 - 1416. [Abstract] [Full Text] [PDF]

				N. L. Kanagy Increased vascular responsiveness to alpha 2-adrenergic stimulation during NOS inhibition-induced hypertension Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2756 - H2764. [Abstract] [Full Text] [PDF]

				A. Montanari, E. Tateo, E. Fasoli, D. Giberti, P. Perinotto, A. Novarini, and P. Dall'Aglio Angiotensin II Blockade Does Not Prevent Renal Effects of L-NAME in Sodium-Repleted Humans Hypertension, September 1, 1997; 30(3): 557 - 562. [Abstract] [Full Text]