ABSTRACT
The effect of DL-propranolol on NO release in perfused rat hindquarters was studied by using oxyhemoglobin as a capture system to allow the quantitative assay of NO production. In some experiments the stable prostacyclin metabolite 6-keto-PGF1 alpha (6-keto) was simultaneously assayed. We observed that: (1) DL-propranolol induced an increase in NO and 6-keto release. The dextro isomer was inactive; (2) DL-propranolol-induced NO release was only slightly reduced by acetylsalicylic acid in a concentration that inhibits prostacyclin synthesis, and was abolished by the chemical removal of the endothelium with 3-3 cholamidopropyl dimethylammonium 1-propane sulphonate (CHAPS) applied before or during stimulation; (3) NG-nitro-L-arginine blocked DL-propranolol-induced NO production, an effect that was antagonized by L-arginine but not by its dextro isomer.
Subject(s)
Endothelium, Vascular/physiology , Nitric Oxide/metabolism , Propranolol/pharmacology , 6-Ketoprostaglandin F1 alpha/metabolism , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Aspirin/pharmacology , Atropine/pharmacology , Carbachol/pharmacology , Cholic Acids/pharmacology , Epoprostenol/metabolism , Male , Nitroarginine , Oxyhemoglobins/metabolism , Rats , Rats, Inbred StrainsABSTRACT
The effect of increasing magnesium concentration (0.61, 1.22, 2.44 and 4.88 mM) on the acetylcholine dose-response curve of isolated strips of the longitudinal muscle of the guinea pig ileum was studied qualitatively and quantitatively in Krebs solution with 2.55 and 5.10 mM calcium. The quantitative study was based on a hypothesis assuming the competition of both ions for a common binding site in the cell "stores" from which the calcium is mobilized following cholinergic receptor activation. The theoretical equations fit the experimental data and allow the calculation of the calcium and magnesium equilibrium constants. As a cross-check two groups of experiments were done to compare the influence on the acetylcholine dose-response curve of a gradual decrease of extracellular calcium either without or with magnesium. The amounts of magnesium used were those theoretically suitable for maintaining a constant amount of calcium in the hypothetical cell "stores". The results agreed with the predictions form the model proposed thus confirming both the hypothesis and the values obtained for the calcium and magnesium equilibrium constants.
Subject(s)
Calcium/antagonists & inhibitors , Magnesium/antagonists & inhibitors , Muscle, Smooth/drug effects , Acetylcholine/pharmacology , Animals , Binding Sites/drug effects , Calcium/pharmacology , Dose-Response Relationship, Drug , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Magnesium/pharmacology , Models, Theoretical , Muscle Contraction/drug effectsABSTRACT
Colchicine and emetine administered locally in the hind paw of the rats increased markedly the capillar permeability. The action may be strongly inhibited by methysergide (0.2 mug). Mepyramine (0.5 mug) is not so active and indomethacine (1 mg/kg per os), even less. As some prostaglandines release serotonine and histamine (8) it is possible that some liberation of these mediators may be attribuable to a previous release of prostaglandines, but the experiments suggest also the possibility of a direct and concomitant release of those two mediators by the alkaloids assayed.
