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Comparison of effect of endothelin antagonism and angiotensin-converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N omega-nitro-L-arginine methyl ester. Correlation with topography of vascular endothelin-1 gene expression.
Hypertension. 1996 Aug; 28(2):188-95.H

Abstract

Inhibition of nitric oxide synthase by L-arginine analogues such as N omega-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.

Authors+Show Affiliations

Medical Research Council Multidisciplinary Research Group on Hypertension, University of Montréal, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8707380

Citation

Li, J S., et al. "Comparison of Effect of Endothelin Antagonism and Angiotensin-converting Enzyme Inhibition On Blood Pressure and Vascular Structure in Spontaneously Hypertensive Rats Treated With N omega-nitro-L-arginine Methyl Ester. Correlation With Topography of Vascular Endothelin-1 Gene Expression." Hypertension (Dallas, Tex. : 1979), vol. 28, no. 2, 1996, pp. 188-95.
Li JS, Deng LY, Grove K, et al. Comparison of effect of endothelin antagonism and angiotensin-converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N omega-nitro-L-arginine methyl ester. Correlation with topography of vascular endothelin-1 gene expression. Hypertension. 1996;28(2):188-95.
Li, J. S., Deng, L. Y., Grove, K., Deschepper, C. F., & Schiffrin, E. L. (1996). Comparison of effect of endothelin antagonism and angiotensin-converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N omega-nitro-L-arginine methyl ester. Correlation with topography of vascular endothelin-1 gene expression. Hypertension (Dallas, Tex. : 1979), 28(2), 188-95.
Li JS, et al. Comparison of Effect of Endothelin Antagonism and Angiotensin-converting Enzyme Inhibition On Blood Pressure and Vascular Structure in Spontaneously Hypertensive Rats Treated With N omega-nitro-L-arginine Methyl Ester. Correlation With Topography of Vascular Endothelin-1 Gene Expression. Hypertension. 1996;28(2):188-95. PubMed PMID: 8707380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of effect of endothelin antagonism and angiotensin-converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N omega-nitro-L-arginine methyl ester. Correlation with topography of vascular endothelin-1 gene expression. AU - Li,J S, AU - Deng,L Y, AU - Grove,K, AU - Deschepper,C F, AU - Schiffrin,E L, PY - 1996/8/1/pubmed PY - 1996/8/1/medline PY - 1996/8/1/entrez SP - 188 EP - 95 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 28 IS - 2 N2 - Inhibition of nitric oxide synthase by L-arginine analogues such as N omega-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. SN - 0194-911X UR - https://www.unboundmedicine.com/medline/citation/8707380/Comparison_of_effect_of_endothelin_antagonism_and_angiotensin_converting_enzyme_inhibition_on_blood_pressure_and_vascular_structure_in_spontaneously_hypertensive_rats_treated_with_N_omega_nitro_L_arginine_methyl_ester__Correlation_with_topography_of_vascular_endothelin_1_gene_expression_ L2 - https://www.ahajournals.org/doi/10.1161/01.hyp.28.2.188?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -