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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. 1997 Jan 07; 95(1):240-4.Circ

Abstract

BACKGROUND

Vascular expression of the endothelin-1 gene may be associated with severe vascular hypertrophy. Because in rats, inhibition of NO synthase with the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) induces blood pressure elevation associated with little cardiovascular hypertrophy, we studied vascular endothelin-1 gene expression in L-NAME-treated rats and the effects of chronic endothelin antagonism.

METHODS AND RESULTS

Sprague-Dawley rats received 100 mg.kg-1.d-1 L-NAME in their drinking water for 3 weeks. Systolic blood pressure rose to 189 +/- 3 mm Hg (P < .001 versus control rats). By Northern blot analysis, endothelin-1 mRNA levels were similar in aortas and mesenteric arteries of control and L-NAME-treated rats. The blood pressure of L-NAME hypertensive rats treated with the ETA-selective endothelin receptor antagonist A-127722 for 3 weeks at a low dose (10 mg.kg-1.d-1) and a high dose (30 mg.kg-1.d-1) was not different from that of rats receiving L-NAME but not the endothelin antagonist. Treatment with the ACE inhibitor cilazapril lowered the blood pressure of L-NAME-treated rats equally whether or not they were receiving the ETA antagonist.

CONCLUSIONS

These results indicate that the endothelin system does not participate to an important degree in the mechanisms leading to elevated blood pressure after chronic NO synthase inhibition with L-NAME in normal rats. In the chronic model of L-NAME-induced hypertension, blockade of the renin-angiotensin system does not unmask an endothelin-dependent vasopressor tone. In addition, either NO does not regulate vascular endothelin-1 gene expression or L-NAME exerts an inhibitory effect on endothelin expression in blood vessels.

Authors+Show Affiliations

Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8994442

Citation

Sventek, P, et al. "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, vol. 95, no. 1, 1997, pp. 240-4.
Sventek P, Turgeon A, Schiffrin EL. 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. 1997;95(1):240-4.
Sventek, P., Turgeon, A., & Schiffrin, E. L. (1997). 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, 95(1), 240-4.
Sventek P, Turgeon A, Schiffrin EL. 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. 1997 Jan 7;95(1):240-4. PubMed PMID: 8994442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sventek,P, AU - Turgeon,A, AU - Schiffrin,E L, PY - 1997/1/7/pubmed PY - 1997/1/7/medline PY - 1997/1/7/entrez SP - 240 EP - 4 JF - Circulation JO - Circulation VL - 95 IS - 1 N2 - BACKGROUND: Vascular expression of the endothelin-1 gene may be associated with severe vascular hypertrophy. Because in rats, inhibition of NO synthase with the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) induces blood pressure elevation associated with little cardiovascular hypertrophy, we studied vascular endothelin-1 gene expression in L-NAME-treated rats and the effects of chronic endothelin antagonism. METHODS AND RESULTS: Sprague-Dawley rats received 100 mg.kg-1.d-1 L-NAME in their drinking water for 3 weeks. Systolic blood pressure rose to 189 +/- 3 mm Hg (P < .001 versus control rats). By Northern blot analysis, endothelin-1 mRNA levels were similar in aortas and mesenteric arteries of control and L-NAME-treated rats. The blood pressure of L-NAME hypertensive rats treated with the ETA-selective endothelin receptor antagonist A-127722 for 3 weeks at a low dose (10 mg.kg-1.d-1) and a high dose (30 mg.kg-1.d-1) was not different from that of rats receiving L-NAME but not the endothelin antagonist. Treatment with the ACE inhibitor cilazapril lowered the blood pressure of L-NAME-treated rats equally whether or not they were receiving the ETA antagonist. CONCLUSIONS: These results indicate that the endothelin system does not participate to an important degree in the mechanisms leading to elevated blood pressure after chronic NO synthase inhibition with L-NAME in normal rats. In the chronic model of L-NAME-induced hypertension, blockade of the renin-angiotensin system does not unmask an endothelin-dependent vasopressor tone. In addition, either NO does not regulate vascular endothelin-1 gene expression or L-NAME exerts an inhibitory effect on endothelin expression in blood vessels. SN - 0009-7322 UR - https://www.unboundmedicine.com/medline/citation/8994442/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_ L2 - https://www.ahajournals.org/doi/10.1161/01.cir.95.1.240?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -