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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
Author(s) -
López Ruth M.,
Ortíz Cindy S.,
Ruíz Antonio,
Vélez Juan M.,
Castillo Carlos,
Castillo Enrique F.
Publication year - 2004
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2004.00294.x
Subject(s) - phenylephrine , aorta , nitric oxide , endothelium , endocrinology , isometric exercise , medicine , thoracic aorta , vascular smooth muscle , nitroarginine , acetylcholine , vasoconstriction , blood vessel , chemistry , nitric oxide synthase , smooth muscle , blood pressure
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 m m ) 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 × 10 −6 m )‐ and K + (80 m m )‐induced contractions and 45 Ca 2+ influxes were significantly reduced. In Ca 2+ ‐free medium (0.1 m m EDTA), on the contrary, the transient contractions obtained by either phenylephrine (1 × 10 −6 m ) or caffeine (1 × 10 −2 m ), or the sustained contractions induced by 12‐ o ‐tetradecanoylphorbol‐13‐acetate (1 × 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.