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Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester.
Fundam Clin Pharmacol. 2004 Dec; 18(6):669-77.FC

Abstract

In this study, we aimed to elucidate whether the daily hypertensive dose of long-term N(G)-nitro-l-arginine methyl ester (l-NAME) treatment, could make a difference between endothelial and smooth muscle functions in rat thoracic aorta. We test the hypothesis that high-dose, long-term l-NAME treatment has a depressive effect on vascular smooth muscle contractile activity which is not related with nitric oxide (NO) synthesis inhibition. After 14 days of treatment, isometric tension and (45)Ca(2+) influx were measured in aortic tissues isolated from l-NAME(10) and l-NAME(100) hypertensive (10 and 100 mg/kg/day, systolic blood pressures 167 +/- 7 and 172 +/- 10 mmHg, respectively) and control normotensive rats (132 +/- 7 mmHg). In l-NAME(10)- and l-NAME(100)-treated rats, acetylcholine-induced relaxation in aortic rings was suppressed with no significant difference between the treatments. l-NAME(100) (but not l-NAME(10)) treatment, significantly inhibited contractile responses to phenylephrine, angiotensin II, and K(+) (80 mm) in endothelium-intact tissues. The effect of l-NAME(100) on phenylephrine-induced contractile responses was not observed after 3 days of treatment. In endothelium-denuded aortic tissues of l-NAME(100) (but not l-NAME(10))-treated rats, phenylephrine (1 x 10(-6) m)- and K(+) (80 mm)-induced contractions and (45)Ca(2+) influxes were significantly reduced. In Ca(2+)-free medium (0.1 mm EDTA), on the contrary, the transient contractions obtained by either phenylephrine (1 x 10(-6) m) or caffeine (1 x 10(-2) m), or the sustained contractions induced by 12-o-tetradecanoylphorbol-13-acetate (1 x 10(-6) m; a protein kinase C activator) in endothelium-denuded aortic rings, were not modified by both l-NAME treatments. These results indicate that in aortic rings from l-NAME hypertensive rats, low and high doses, long-term l-NAME administration may be associated with equivalent inhibition in NO-dependent vasodilator tone (corresponding to equivalent hypertension values); whereas only high-dose, long-term l-NAME administration produces an endothelium-independent decrease in vasocontrictor activity, at least partly explained by a reduction in extracellular Ca(2+) influx.

Authors+Show Affiliations

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, Col. Casco de Santo Tomás, CP 11340, México, D.F., México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15548238

Citation

López, Ruth M., et al. "Impairment of Smooth Muscle Function of Rat Thoracic Aorta in an Endothelium-independent Manner By Long-term Administration of N(G)-nitro-L-arginine Methyl Ester." Fundamental & Clinical Pharmacology, vol. 18, no. 6, 2004, pp. 669-77.
López RM, Ortíz CS, Ruíz A, et al. Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester. Fundam Clin Pharmacol. 2004;18(6):669-77.
López, R. M., Ortíz, C. S., Ruíz, A., Vélez, J. M., Castillo, C., & Castillo, E. F. (2004). Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester. Fundamental & Clinical Pharmacology, 18(6), 669-77.
López RM, et al. Impairment of Smooth Muscle Function of Rat Thoracic Aorta in an Endothelium-independent Manner By Long-term Administration of N(G)-nitro-L-arginine Methyl Ester. Fundam Clin Pharmacol. 2004;18(6):669-77. PubMed PMID: 15548238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester. AU - López,Ruth M, AU - Ortíz,Cindy S, AU - Ruíz,Antonio, AU - Vélez,Juan M, AU - Castillo,Carlos, AU - Castillo,Enrique F, PY - 2004/11/19/pubmed PY - 2005/3/17/medline PY - 2004/11/19/entrez SP - 669 EP - 77 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 18 IS - 6 N2 - In this study, we aimed to elucidate whether the daily hypertensive dose of long-term N(G)-nitro-l-arginine methyl ester (l-NAME) treatment, could make a difference between endothelial and smooth muscle functions in rat thoracic aorta. We test the hypothesis that high-dose, long-term l-NAME treatment has a depressive effect on vascular smooth muscle contractile activity which is not related with nitric oxide (NO) synthesis inhibition. After 14 days of treatment, isometric tension and (45)Ca(2+) influx were measured in aortic tissues isolated from l-NAME(10) and l-NAME(100) hypertensive (10 and 100 mg/kg/day, systolic blood pressures 167 +/- 7 and 172 +/- 10 mmHg, respectively) and control normotensive rats (132 +/- 7 mmHg). In l-NAME(10)- and l-NAME(100)-treated rats, acetylcholine-induced relaxation in aortic rings was suppressed with no significant difference between the treatments. l-NAME(100) (but not l-NAME(10)) treatment, significantly inhibited contractile responses to phenylephrine, angiotensin II, and K(+) (80 mm) in endothelium-intact tissues. The effect of l-NAME(100) on phenylephrine-induced contractile responses was not observed after 3 days of treatment. In endothelium-denuded aortic tissues of l-NAME(100) (but not l-NAME(10))-treated rats, phenylephrine (1 x 10(-6) m)- and K(+) (80 mm)-induced contractions and (45)Ca(2+) influxes were significantly reduced. In Ca(2+)-free medium (0.1 mm EDTA), on the contrary, the transient contractions obtained by either phenylephrine (1 x 10(-6) m) or caffeine (1 x 10(-2) m), or the sustained contractions induced by 12-o-tetradecanoylphorbol-13-acetate (1 x 10(-6) m; a protein kinase C activator) in endothelium-denuded aortic rings, were not modified by both l-NAME treatments. These results indicate that in aortic rings from l-NAME hypertensive rats, low and high doses, long-term l-NAME administration may be associated with equivalent inhibition in NO-dependent vasodilator tone (corresponding to equivalent hypertension values); whereas only high-dose, long-term l-NAME administration produces an endothelium-independent decrease in vasocontrictor activity, at least partly explained by a reduction in extracellular Ca(2+) influx. SN - 0767-3981 UR - https://www.unboundmedicine.com/medline/citation/15548238/Impairment_of_smooth_muscle_function_of_rat_thoracic_aorta_in_an_endothelium_independent_manner_by_long_term_administration_of_N_G__nitro_L_arginine_methyl_ester_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0767-3981&date=2004&volume=18&issue=6&spage=669 DB - PRIME DP - Unbound Medicine ER -