Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta. 1996

D N Criddle, and R S de Moura, and I A Greenwood, and W A Large
Departmento de Farmacologia, Centro Biomédico-IB, Universidade do Estado do Rio de Janeiro, Brasil.

1. The effects of niflumic acid, an inhibitor of calcium-activated chloride channels, were compared with the actions of the calcium channel antagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta. 2. The cumulative concentration-effect curve to noradrenaline (NA) was depressed by both nifedipine and niflumic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 microM) produced by 10 microM niflumic acid (38%) was similar to the effect of 1 microM nifedipine (39%). 3. Contractions to brief applications (30 s) of 1 microM NA were inhibited by 55% and 62% respectively by 10 microM niflumic acid and 1 microM nifedipine. 4. In the presence of 0.1 microM nifedipine, niflumic acid (10 microM) produced no further inhibition of the NA-evoked contractions. Thus, the actions of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contraction induced by 1 microM NA was not inhibited by niflumic acid (10 microM) and therefore this agent does not reduce the amount of calcium released from the intracellular store or reduce the sensitivity of the contractile apparatus to calcium. 6. Niflumic acid 10 microM did not inhibit the contractions produced by KCl (up to 120 mM) which were totally blocked by nifedipine. Contractions induced by 25 mM KCl were completely inhibited by 1 microM levcromakalim but were unaffected by niflumic acid. 7. It was concluded that niflumic acid produces selective inhibition of a component of NA-evoked contraction which is probably mediated by voltage-gated calcium channels. These data are consistent with a model in which NA stimulates a calcium-activated chloride conductance which leads to the opening of voltage-gated calcium channels to produce contraction.

UI MeSH Term Description Entries
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D009544 Niflumic Acid An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis. Donalgin,Flunir,Niflactol,Niflugel,Nifluril,Acid, Niflumic
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001013 Aorta, Thoracic The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA. Aorta, Ascending,Aorta, Descending,Aortic Arch,Aortic Root,Arch of the Aorta,Descending Aorta,Sinotubular Junction,Ascending Aorta,Thoracic Aorta,Aortic Roots,Arch, Aortic,Ascending Aortas,Junction, Sinotubular,Root, Aortic,Sinotubular Junctions

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