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 Li, J.-S. Articles by Schiffrin, E. L. Search for Related Content PubMed PubMed Citation Articles by Li, J.-S. Articles by Schiffrin, E. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE NITRIC OXIDE Medline Plus Health Information High Blood Pressure

(Hypertension. 1996;28:188-195.)
© 1996 American Heart Association, Inc.

Articles

Comparison of Effect of Endothelin Antagonism and Angiotensin-Converting Enzyme Inhibition on Blood Pressure and Vascular Structure in Spontaneously Hypertensive Rats Treated With N-Nitro-L-Arginine Methyl Ester

Correlation With Topography of Vascular Endothelin-1 Gene Expression

Jin-S. Li; Li Y. Deng; Kevin Grove; Christian F. Deschepper; Ernesto L. Schiffrin

the Medical Research Council Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal (Canada).

Inhibition of nitric oxide synthase by L-arginine analogues such as N-nitro-L-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHR) is associated with malignant hypertension and enhanced expression of the endothelin-1 gene in some blood vessels. In this study, SHR treated chronically with L-NAME (SHR–L-NAME) were given the angiotensin I–converting enzyme inhibitor cilazapril or the endothelin-A/endothelin-B receptor antagonist bosentan for 3 weeks. Systolic pressure was lowered slightly by cilazapril (213±2 versus 229±2 mm Hg in untreated SHR–L-NAME, P<.01) but was not significantly lowered by bosentan (223±2 mm Hg). Hypertrophy of aorta and small arteries (coronary, renal, mesenteric, and femoral) was decreased by cilazapril treatment and unaffected by bosentan. Expression of the endothelin-1 gene was evaluated in SHR–L-NAME by in situ hybridization histochemistry, which showed that endothelin-1 expression was enhanced in the endothelium of aorta but not in small mesenteric arteries in these rats. The absence of enhancement of endothelin-1 gene expression in small arteries may account for the absence of increased severity of hypertrophy of small vessels in SHR–L-NAME and may be a mechanism whereby L-NAME inhibits cardiovascular growth. These results suggest that in the absence of enhanced small-artery endothelin-1 expression, endothelin antagonism does not lower blood pressure. The blood pressure–lowering effect of angiotensin I–converting enzyme inhibition suggests a role for the renin-angiotensin system in the malignant form of hypertension that develops in SHR treated with L-NAME.

Key Words: aorta • resistance vessels • nitric oxide • endothelium-derived factor • receptors, endothelin

This article has been cited by other articles:

				G. L. Baumbach, C. D. Sigmund, and F. M. Faraci Structure of Cerebral Arterioles in Mice Deficient in Expression of the Gene for Endothelial Nitric Oxide Synthase Circ. Res., October 15, 2004; 95(8): 822 - 829. [Abstract] [Full Text] [PDF]

				Y. Zhang, D. Carreras, and A. J. de Bold Discoordinate re-expression of cardiac fetal genes in N{omega}-nitro-L-arginine methyl ester (L-NAME) hypertension Cardiovasc Res, January 1, 2003; 57(1): 158 - 167. [Abstract] [Full Text] [PDF]

				H. Ono, Y. Ono, A. Takanohashi, H. Matsuoka, and E. D. Frohlich Apoptosis and Glomerular Injury After Prolonged Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats Hypertension, December 1, 2001; 38(6): 1300 - 1306. [Abstract] [Full Text] [PDF]

				C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, and J. A. Panza Increased activity of endogenous endothelin in patients with hypercholesterolemia J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1483 - 1488. [Abstract] [Full Text] [PDF]

				Y. Ono, H. Ono, H. Matsuoka, T. Fujimori, and E. D. Frohlich Apoptosis, Coronary Arterial Remodeling, and Myocardial Infarction After Nitric Oxide Inhibition in SHR Hypertension, October 1, 1999; 34(4): 609 - 616. [Abstract] [Full Text] [PDF]

				A. Kurtz and C. Wagner Role of nitric oxide in the control of renin secretion Am J Physiol Renal Physiol, December 1, 1998; 275(6): F849 - F862. [Abstract] [Full Text] [PDF]

				D. Fraccarollo, K. Hu, P. Galuppo, P. Gaudron, and G. Ertl Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling Circulation, December 2, 1997; 96(11): 3963 - 3973. [Abstract] [Full Text]

				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]

				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]