Tags

Type your tag names separated by a space and hit enter

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.

Links

Publisher Full Text
Aggregator Full Text

Authors+Show Affiliations

López RM
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.
Ortíz CS
No affiliation info available
Ruíz A
No affiliation info available
Vélez JM
No affiliation info available
Castillo C
No affiliation info available
Castillo EF
No affiliation info available

MeSH

Adrenergic alpha-AgonistsAnimalsAorta, ThoracicBlood PressureCalciumCalcium RadioisotopesCyclooxygenase InhibitorsDose-Response Relationship, DrugEndothelium, VascularHypertensionIn Vitro TechniquesMaleMuscle ContractionMuscle, Smooth, VascularNG-Nitroarginine Methyl EsterNitric OxidePotassiumRatsRats, WistarVasoconstrictor AgentsVasodilator Agents

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 -