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Biomedical subjects

A Meli

Publications and source records attributed to A Meli.

At least 235 records · Page 13Linked to original sources
PubMed1983

Octylonium bromide: a smooth muscle relaxant which interferes with calcium ions mobilization.

A series of "in vitro" experiments have been carried out to determine the mechanisms(s) responsible for the smooth muscle relaxant properties exhibited by octylonium bromide. Unlike N-butyl-scopolammonium bromide, octylonium bromide possesses both competitive and non competitive antimuscarinic and antihistaminic properties. Pretreatment of ileal segments with dibenamie, which destroyed muscarinic spare receptors, revealed the non competitive nature of octylonium bromide antagonism. The competitive antagonism toward BaCl2-induced contraction of rat ileum and aorta suggested that octylonium bromide interferes with Ca++ mobilization. As compared with verapamil a known Ca++ entry blocker and unlike it, octylonium bromide is more effective in antagonizing Ca++-induced contraction in K+ depolarized rat colon than aorta. Both octylonium bromide and verapamil reduced in a concentration-dependent manner the tonic contraction produced by exposure to high K+ of rat duodenum and rabbit ear artery. Both octylonium bromide and verapamil antagonized carbachol-induced phasic plus sustained tonic contraction of rat colon in high K+ Ca++-free medium. Unlike octylonium bromide, verapamil antagonized the phasic contraction only and inhibition of the overall contraction did not exceed 60%. Unlike verapamil, octylonium bromide antagonized norepinephrine-induced contraction of rabbit ear artery in high K+ C++-free medium. Interference with mobilization of cellular and extracellular Ca++ pools produced by different neurohormones is likely to be the mechanism responsible for octylonium bromide smooth muscle relaxant properties in both animals and humans.

Animals↗
PubMed1982

An in vivo procedure for estimating spasmolytic activity in the rat by measuring smooth muscle contractions to topically applied acetylcholine.

An in vivo procedure for evaluating potential organ selectivity of spasmolytics has been developed. This involves the determination of comparative potencies, expressed as DR10 of spasmolytics against contractions induced by topical application of acetylcholine on rat colon, rectum and urinary bladder. Experiments with two well known spasmolytics, namely N-butyl-scopolammonium bromide and dicyclomine HCl yielded results consistent with data reported in the literature. This procedure provides a rapid, inexpensive and rather accurate estimate of organ selectivity of spasmolytics.

Acetylcholine↗
PubMed1982

A simple procedure for assessing norepinephrine-induced cellular and extracellular Ca++ mobilization in rabbit ear artery.

Although the response of vascular smooth muscle to norepinephrine (NE) is biphasic in nature, there is no simple procedure for the separate quantitative analysis of intracellular and extracellular Ca++ dependent NE-induced contractions. Intraluminal NE in high-K+Ca++-free medium produces a dose-dependent contraction which is selectively antagonized by procaine (1 X 10(-3) M--5 X 10(-3) M). Subsequent reperfusion with normal Krebs of NE-pretreated arterial segments results in a dose-dependent contraction which is strictly related to extracellular Ca++ concentration and is selectively inhibited by verapamil (5 X 10(-6) M--5 X 10(-5) M). These results can be interpreted as an indication that this procedure is suitable for the separate analysis of the capability of vasoactive drugs to differentially mobilize cellular and extracellular Ca++ pools in perfused rabbit ear artery preparations.

Animals↗
PubMed1982

Modulation by beta-adrenoreceptors of spontaneous contractions of rat urinary bladder.

1 Propranolol (0.1 mg/kg i.v.) but not metoprolol (0.2 mg/kg i.v.) pretreatment increased the spontaneous motility triggered by progressive filling of rat urinary bladder without a concomitant effect on bladder capacity, except at high filling volumes. Compared to controls, the spontaneous motility of urinary bladder in propranolol pretreated rats displayed a higher frequency, indicating the existence of a tonic sympathetic inhibition. 2 beta-adrenoreceptor stimulation by isoprenaline (0.1-10 microgram/kg i.v.) or terbutaline (0.1-1 mg/kg i.v.) in vivo produced a dose dependent inhibition of bladder spontaneous motility which was antagonized by propranolol (0.1 mg/kg i.v.) but not by metoprolol (0.2 mg/kg i.v.). Propranolol (0.2 mg/kg i.v.) pretreatment did not antagonize the inhibition of bladder motility produced by intravenous papaverine (0.5 mg/kg). 3 Propranolol (0.1 mg/kg i.v.) significantly antagonized the isoprenaline-induced tachycardia (beta 1 mediated) and fall in diastolic blood pressure (beta 2 mediated) while metoprolol (0.2 mg/kg i.v.) antagonism was confined to beta 1 mediated responses. 4 Isoprenaline (0.25-1.5 microM) inhibited in a concentration dependent manner field stimulation induced contractions of rat detrusor muscle strips as did tetrodotoxin (0.5 microM). Hexamethonium (50 microM) had no inhibitory effect. 5 Our in vivo findings support the view that beta 2-adrenoreceptors are responsible for modulating bladder motility mainly by suppressing the onset of spontaneous contractions.

Animals↗
PubMed1982

Age-related protective role of parasympathetic nervous system against hypercalcaemia-induced ventricular arrhythmias in the rat.

Time of appearance of extrasystoles, ventricular fibrillation, and cardiac arrest were monitored in urethane-anaesthetized rats of different ages following CaCl2 infusion. Ca++ required to produce ventricular arrhythmias was significantly higher in younger than in older animals. Bilateral vagotomy or atropine treatment significantly reduced Ca++ requirements for production of arrhythmias in younger but not in older animals. These findings support the hypothesis of vagally mediated age-related antagonism toward Ca++-induced ventricular arrhythmias. This suggests that young subjects are less prone to develop ventricular rhythm disturbances as a result of hypercalcaemic states.

Age Factors↗
PubMed1982

The effects of nifedipine and verapamil on spontaneous and carbachol-stimulated contractions of rat urinary bladder "in vivo".

The effects of nifedipine and verapamil on spontaneous and carbachol-induced contractions of rat urinary bladder have been studied after intravenous administration. Both nifedipine and verapamil delayed the onset of spontaneous contractions in a dose-dependent manner, but nifedipine on the contrary of verapamil only slightly antagonized the intensity of spontaneous contractions and of carbachol contracture. These results suggest that the effects of verapamil on rat urinary bladder "in vivo" are different from those of nifedipine.

Animals↗
PubMed1981

The anesthetized guinea pig as a versatile pharmacological test object.

An anesthetized animal preparation suitable for testing the pharmacological properties of a variety of potentially effective new compounds is described. The advantage of such a procedure as an useful tool to determine the pharmacodynamic profile of the new agents is described in detail.

Adrenergic beta-Antagonists↗
PubMed1981

The role of the local anaesthetic properties of beta-adrenoceptor blocking agents in antagonizing CaCl2-induced arrhythmias in the rat.

1 Eight beta-adrenoceptor blocking agents were compared for their ability to antagonize arrhythmias induced by bolus injections of CaCl2 in rats. 2 Only those beta-blockers possessing local anaesthetic properties were effective in antagonizing this type of arrhythmia and there was a highly significant correlation between antiarrhythmic and local anaesthetic properties. 3 Effects on adrenoceptors seem to play only a minor role in the genesis of this type of arrhythmia.

Adrenergic beta-Antagonists↗
PubMed1979

Influence of fasting and cimetidine on the relationship between ulcerogenic and anti-inflammatory properties of indomethacin.

1 Further studies have been carried out on the relationship between ulcerogenic and anti-inflammatory properties of indomethacin in the rat. 2 Fasting, which increases gastric and reduces intestinal lesions, enhances the anti-oedema properties of indomethacin. 3 The presence of intestinal lesions, greatly increases the anti-oedema properties of indomethacin through a mechanism(s) unrelated to the specific pharmacological properties of this drug. 4 Studies with cimetidine, have shown that the enhancement of anti-oedema effects produced by fasting are due to specific pharmacological properties of indomethacin rather than to non specific effects related to the presence of gastric ulcers. 5 The greater anti-inflammatory effects of indomethacin in fasted as compared to fed animals must be attributed to the greater amount of indomethacin available for tissue distribution rather than other mechanisms associated with free fatty acid mobilization. 6 In view of ineffectiveness in preventing intestinal lesions, the use of cimetidine for prevention or reduction of indomethacin-induced gastrointestinal disturbances in humans is contraindicated.

Animals↗
PubMed1978

Further investigations of indomethacin and intestinal ulcers in the rat.

The lower incidence of indomethacin-induced intestinal ulcers in fasted as compared to fed rats must be attributed to factor(s) other than changes in bile flow and composition. Experimental evidence and data in the literature rather suggest that the amount of food present in the gastrointestinal tract at the time indomethacin was given may influence ulcer formation by affecting the duration and degree enterohepatic circulation of this compound.

Animals↗