Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Dec 1988
Train-of-four fade during neuromuscular blockade induced by tubocurarine, succinylcholine or alpha-bungarotoxin in the rat isolated hemidiaphragm.
1. Nerve-evoked maximal twitches (T1, T2, T3, T4) of the rat isolated hemidiaphragm to train-of-four (TOF) stimulation (2 Hz X 2 s) were recorded continuously in the absence or presence of tubocurarine (1.5 mumol/l), succinylcholine (40 mumol/l) or alpha-bungarotoxin (1 mumol/l). The T1 and T4 response-time profiles for the three drugs were analysed with respect to amplitude depression and the TOF ratio (T4/T1) during the development of and recovery from neuromuscular blockade. 2. ⋯ Fade is therefore not simply a consequence of postjunctional cholinoceptor blockade. 3. Succinylcholine produced T1 block with only moderate TOF fade; similar recovery rates from 90% T1 block to control levels were obtained for T1 and the TOF ratio. 4. alpha-Bungarotoxin produced irreversible and complete neuromuscular blockade during which TOF fade was virtually absent. 5. The results obtained in this study closely resemble those from other similar studies in animals and in humans and clearly demonstrate that the rat isolated hemidiaphragm is a suitable in vitro model for time course studies on TOF fade.
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Clin. Exp. Pharmacol. Physiol. · May 1988
Inhibition of vasodilatation by methylene blue in large and small arteries of the dog hindlimb in vivo.
1. Injection of acetylcholine (ACh, 0.0005-2 micrograms/kg) or glyceryl trinitrate (GTN, 0.01-20 micrograms/kg) into the femoral artery increased femoral artery diameter, femoral blood flow and heart rate, and reduced femoral vascular resistance and systemic arterial blood pressure in anaesthetized dogs. The intravenous (i.v.) injection of ACh (2 micrograms/kg) produced a small decrease in systemic arterial pressure and an increase in heart rate, but did not dilate the hindlimb vessels. 2. ⋯ This selective potentiation of ACh-induced hypotension was not affected by autonomic ganglion blockade with hexamethonium (25 mg/kg, i.v.). 4. These results suggest that both ACh- and GTN-induced vasodilatation in vivo occurs through a mechanism involving guanylate cyclase activation in large arteries and resistance vessels in the dog hindlimb. Methylene blue inhibited the local vasodilator actions of ACh in the femoral vasculature despite potentiating the systemic depressor response to that agent.
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Clin. Exp. Pharmacol. Physiol. · Mar 1988
Randomized Controlled Trial Clinical TrialChange in blood pressure in relation to change in nutrients effected by manipulation of dietary sodium and potassium.
1. As part of a study investigating the effect of dietary alterations of sodium and potassium intake on blood pressure, the changes in nutrients that occurred with dietary intervention were determined. 2. Mild hypertensive subjects were randomized to one of four dietary intervention groups: control; high potassium; low sodium; low sodium, high potassium. ⋯ The reduction of the dietary sodium/potassium ratio correlated with a reduction in the urinary sodium/potassium ratio. This was the best predictor for change in diastolic pressure in all groups, suggesting that reduction in the sodium/potassium ratio contributed to the fall in blood pressure. 7. Reduction of sodium intake and increase in potassium intake by dietary means caused a reduction in blood pressure which does not appear to be due to alteration of other measured dietary constituents.
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Clin. Exp. Pharmacol. Physiol. · Nov 1984
Canine nonresponders to alveolar hypoxic vasoconstriction and quantitative restoration of the response by aspirin I-3.
Hypoxic pulmonary vasoconstriction is characterized by considerable variability in rate of response (pulmonary vascular resistance [PVR] as a function of time under hypoxia). To further define this response, forty-five closed chest dogs were anaesthetized (pentobarbitone sodium), intubated, and mechanically ventilated. Constant left lower lobar pulmonary artery flow was maintained through a balloon tipped 14F catheter via an extracorporeal pump at a rate to achieve lobar pulmonary artery pressure (Plobar) equal to main pulmonary artery pressure (PPA) and thereafter held constant. ⋯ The absolute values of PVR reached after plateau for HR and for NR ASA (after ASA) were also not different. Aspirin restored the NR capability to develop pulmonary vasoconstriction in response to alveolar hypoxia. The rate of response and the absolute level of response reached were also restored by aspirin.
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Clin. Exp. Pharmacol. Physiol. · Jan 1982
Comparative StudyFurther comparison of the effects of physostigmine and neostigmine on frog neuromuscular transmission.
1. The effects of physostigmine and neostigmine were compared at frog neuromuscular junctions using intracellular microelectrodes. 2. Both drugs increased the amplitudes of miniature endplate potentials (MEPP) in a dose-dependent manner because of their ability to competitively inhibit cholinesterase activity. 3. ⋯ Similar results were obtained with physostigmine. 6. Neither drug significantly affected MEPP frequency although small decreases were sometimes observed. 7. These results suggest that at the frog neuromuscular junction the effects of neostigmine are explained primarily by its inhibition of cholinesterase, whereas physostigmine are explained primarily by its inhibition of cholinesterase, whereas physostigmine has an additional action on nerve terminals of decreasing nerve-stimulated release of acetylcholine.