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Biomedical subjects

I W Rodger

Publications and source records attributed to I W Rodger.

100 records · Page 6Linked to original sources

Actions of the sympathomimetic bronchodilator, rimiterol (R798), on the cardiovascular, respiratory and skeletal muscle systems of the anaesthetized cat.

1. The actions of rimiterol [erythro(3,4-dihydroxyphenyl, 2-piperidyl methanol hydrobromide)], a new sympathomimetic bronchodilator, have been compared with those of salbutamol and laevoisoprenaline on the heart and lungs, and on contractions of the soleus muscle of cats under chloralose anaesthesia.2. Rimiterol and salbutamol injected intravenously were about equipotent in all tests, and were about 8 times less potent than laevoisoprenaline both in opposing the bronchoconstrictor action of 5-hydroxytryptamine, and in decreasing the tension and degree of fusion of incomplete tetanic contractions of the cat soleus muscle. They were about 19 times less potent than laevoisoprenaline in increasing heart rate.3. The effect on the soleus muscle is considered to be analogous to the muscle tremor that often occurs in man, and the results therefore suggest that systemic administration of bronchodilator doses of rimiterol, like salbutamol, may produce muscle tremor as an unwanted side-effect.4. When equipotent doses to oppose 5-hydroxytryptamine-induced bronchospasm were compared, rimiterol and salbutamol produced less tachycardia than did laevoisoprenaline. In order to match the tachycardia produced by laevoisoprenaline, the doses of rimiterol or salbutamol had to be increased about two and a half times. This safety margin for salbutamol in the cat is considerably less than that reported by others for different species, which suggests that beta(1)- and beta(2)-adrenoceptors may be less clearly differentiated in the cat than they are in other laboratory animals.

Amino Alcohols↗

Pharmacological actions of a new -adrenoceptor agonist, MJ-9184-1, in anaesthetized cats.

1. The effects of (-)-isoprenaline and the new beta-adrenoceptor agonist, MJ-9184-1, on the lungs, on the cardiovascular system, and on slow contracting skeletal muscle have been compared in cats under chloralose anaesthesia.2. Both amines reduced the increases in airways resistance produced by 5-HT, depressed incomplete tetanic contractions of the soleus muscle, lowered the blood pressure and produced an increase in heart rate. In comparison with (-)-isoprenaline, MJ-9184-1 had a long duration of action.3. The effects of MJ-9184-1 and (-)-isoprenaline were antagonized by the beta-adrenoceptor antagonist, propranolol.4. MJ-9184-1 was approximately half as potent as (-)-isoprenaline in its effects on pulmonary resistance and soleus muscle contractility, and one seventh as potent in producing chronotropic effects in the heart.5. These results suggest that MJ-9184-1 possesses some specificity as a beta(2) receptor stimulant.

Adrenergic beta-Agonists↗

Some actions of chandonium iodide, a new short-acting muscle relaxant, in anaesthetized cats and on isolated muscle preparations.

1. The actions of the new skeletal muscle relaxant chandonium (HS310) on the cardiovascular, respiratory and skeletal muscle systems of the cat under chloralose anaesthesia and on chick and rat isolated skeletal muscle preparations have been described. 2. In the cat chandonium exhibited a potent, competitive, non-depolarizing neuromuscular blocking action that was rapid in onset and of short duration. It possessed a selective atropine-like action at the cardiac vagus neuro-effector junction but little or no ganglion blocking activity. Neither adrenergic neurone noralpha-adrenoceptor blocking properties were evident. 3. Unlike tubocurarine, chandonium was without effect on the airways system of the anaesthetized cat. 4. Chandonium possessed weak anticholinesterase action. It is conceivable that this effect may contribute to its short duration of action. 5. The results from these studies suggest that chandonium may have possible clinical applications as a short-acting muscle relaxant.

Acetylcholine↗

Sodium-dependent relaxation in arterial smooth muscle.

1. The effects of isosmotic substitution of choline for sodium on resting tension and on relaxation after noradrenaline-induced contraction was studied in rabbit isolated aortic strips immersed in Hepes-buffered physiologic salt solution (PSS) warmed to 37 degrees C and gassed with 100% O2. 2. Isosmotic substitution of choline for sodium produced a sustained increase in resting tension which effectively prevented any evaluation of the influence of sodium on relaxation. The increase in resting tension was insensitive to 10(-8) mol/l atropine but was abolished by 10 min exposure to calcium-free PSS prior to replacement of sodium. 3. Under sodium-calcium free conditions which eliminated the increase in resting tension observed in sodium-free PSS, stimulation with 10(-5) mol/l noradrenaline initiated contractions that were 55 +/- 7.5% of the control response in normal PSS. Washout of noradrenaline with sodium-calcium-free PSS failed to produce any decrement in tension. However, restoration of the normal sodium resulted in gradual relaxation. 4. These results suggest that sodium is required for relaxation after noradrenaline-induce contraction of arterial smooth muscle.

Animals↗

Direct action of 4-aminopyridine on the contractility of a fast-contracting muscle in the cat.

1. The effects of 4-aminopyridine on the contractility of the fast-contracting tibialis anterior and the slow-contracting soleus muscles of cats under chloralose anaesthesia have been studied. 2. 4-Aminopyridine, in doses of 0.5 mg/kg and above, produced a slowly developing increase in the twitch tension of directly stimulated chronically denervated and of indirectly stimulated innervated tibialis anterior muscles, but had little or no effect on twitches of soleus muscles. The effect of innervated tibialis anterior muscles was more pronounced than that on chronically denervated muscles, but it was nevertheless concluded that the whole effect on innervated muscles was the result of a direct action on the muscle fibres. The simultaneously occurring facilitatory action on neuromuscular transmission, which is manifested in the anti-curare action of 4-aminopyridine, had a faster time-course and occurred in both the tibialis anterior and the soleus muscles. 3. 4-Aminopyridine antagonized dantrolene sodium on on the tibialis anterior muscle but not on the soleus muscle. The antagonism could be described as physiological antagonism since it simply reflected the opposing actions on contractility of the two drugs. 4. 4-Aminopyridine was without effect on maximal tetanic tension of either the tibialis anterior or the soleus muscle. 5. It seems clear from the literature that a species difference exists with regard to the ability of 4-aminopyridine to increase muscle contractility. The results described in this paper show that muscle differences within the same species also exist.

4-Aminopyridine↗

One-month exposure to inhaled endotoxin produces a dose-dependent increase in stored mucosubstances in rat intrapulmonary airways.

This study examined the production of stored mucosubtances in rats after repeated exposure to aerosolized endotoxin, a common contaminant of bioaerosols. Male Fischer 344 rats were exposed to aerosolized saline (sham control) or endotoxin (target concentrations of 0.05, 0.5, and 5.0 micrograms/m3) for 3 h/day, 5 days/week for 4 weeks. Following the final exposure, the left lung of each animal was lavaged and the right lung and nasal cavity were fixed with buffered formalin. Morphometric examination of Alcian blue/Periodic acid Schiffs-stained (AB/PAS) lung sections demonstrated dose-dependent increases in stored intraepithelial mucosubstances in the intrapulmonary airways of endotoxin-exposed rats. Threefold and eightfold increases in stored mucosubstances were observed in generation 5 airways of animals exposed to 0.5 or 5.0 microgram/m3 endotoxin, respectively (p < .05). This mucous cell metaplasia in the intrapulmonary airways was not accompanied by evidence of lung inflammation or increased AB/PAS-staining high molecular weight material in lavage fluid. Furthermore, despite significant deposition of endotoxin aerosols (mass median aerodynamic diameter of 1.9 microns) in the nasal cavity, no significant changes in stored mucosubstances were observed in the nasal septum. In animals repeatedly exposed to 5.0 micrograms/m3 endotoxin and allowed to recover for 1 month, stored mucosubstances in the intrapulmonary airway were still more than fivefold greater than control values. Thus, in rats, repeated exposure to inhaled endotoxin produced a persistent mucous cell metaplasia only in the intrapulmonary airways.

Administration, Inhalation↗