Biomedical subjects

B E Bishop

Publications and source records attributed to B E Bishop.

At least 19 recordsLinked to original sources

PubMed1996

Effects of potassium channel blockers on the action potentials and contractility of the rat right ventricle.

1. The effects of several potassium channel blockers on the action potentials and contractile force of the electrically driven rat right ventricle have been determined. 2. Glibenclamide, which blocks the ATP-sensitive potassium channels, had no effect on the ventricular action potentials or contractile force responses. 3. 4-Aminopyridine, which blocks the Na(+)-activated potassium channels in ventricles, at 0.3-3 mM increased the amplitude and prolonged the action potentials, and also augmented the force responses to cardiac stimulation and to isoprenaline. 4. Clofilium, a selective blocker of the delayed outward rectifying potassium channel, at 0.1 and 0.3 microM prolonged the action potentials. At 0.1 microM, clofilium augmented the cardiac stimulation responses and, at 0.3 microM, clofilium augmented the maximal responses to isoprenaline. At 1 and 3 microM, clofilium had a lesser ability to prolong action potentials and did not alter force responses. 5. Procaine blocks the Na(+)-activated and the delayed outward rectifying potassium channels and, at higher concentrations, sodium channels. Procaine, at 30 microM, prolonged the action potentials and augmented the force responses to isoprenaline, presumably by blocking potassium channels. Procaine, at 1 mM, had no effect on action potentials but reduced the maximal force responses to isoprenaline, probably by blocking sodium channels. 6. Tetraethylammonium blocks the inward rectifying and delayed outward rectifying potassium channels. Tetraethylammonium, at 1 and 3 mM, prolonged the action potentials and augmented all of the force responses; these effects are likely to be predominantly due to blocking the outward rectifying potassium channel. Thus, in the presence of procaine, the effects of tetraethylammonium are predominantly due to the additional blockade of the inward rectifying potassium channel and there were no effects. 7. None of the potassium channel blockers at any of the concentrations tested had arrhythmogenic effects alone or in the presence of isoprenaline. 8. In summary, this study has shown that blockade of the Na(+)-activated and the delayed outward rectifying, but not the ATP-sensitive or inward rectifying, potassium channel is associated with prolongation of the action potentials, augments the contractile force responses, and is not arrhythmogenic on the rat right ventricle. New drugs that block the Na(+)-activated or delayed outward rectifying potassium channel may have potential as positive inotropes in the treatment of heart failure.

4-Aminopyridine↗

PubMed1996

Veratridine augments and BDF 9148 attenuates the spontaneous contractile force of the rat portal vein.

Veratridine and BDF 9148 both increase the force of myocardial contraction but their effects on the contractility of vascular smooth muscle are largely unknown. We have examined the effects of the drugs on the contractile force of the rat portal vein. The force responses of the rat portal vein were not altered by tetrodotoxin (< or = 30 microM) but were augmented by Bay K 8644 (10 nM-10 microM), and attenuated by nifedipine (10 nM-10 micro M). Veratridine slightly reduced the force of spontaneous contractions at concentrations of 0.1-1 microM, then augmented the force at concentrations up to 100 microM. The reduction was prevented by 30 nM tetrodotoxin; a higher concentration of 3 microM prevented the effect of veratridine. Pretreatment with nifedipine at 30 nM reduced the maximum augmentation observed with veratridine. BDF 9148 (0.3-300 microM) attenuated the force and this attenuation was increased in the presence of tetrodotoxin at 3 microM but reversed to an augmentation in the presence of Bay K 8644 at 10 microM. The augmentation produced by BDF 9148 in the presence of Bay K 8644 was reduced by tetrodotoxin at 30 nM. These results suggest that veratridine predominantly opens sodium channels which in turn open voltage-dependent calcium channels to augment the force responses of the rat portal vein, but attenuate force in the presence of sodium-channel blockade with tetrodotoxin. BDF 9148 predominantly closes calcium channels to attenuate the force of the rat portal vein but in the presence of maximum calcium-channel opening with Bay K 8644 augments force probably by opening sodium channels.

Animals↗

PubMed1995

The effects of veratridine and BDF 9148 on the action potentials and contractility of the rat right ventricle.

1. The effects of veratridine, BDF 9148 and lignocaine on the action potentials and contractile force of the electrically-driven rat right ventricle have been determined. 2. Veratridine at 10(-7)-10(-6) M and BDF 9148 at 10(-7)-10(-5) M had no effect on the threshold potential or amplitude but prolonged the ventricular action potentials. 3. In contractility studies, veratridine at 10(-7)-10(-6) M augmented the cardiac stimulation responses and the augmenting effects with 3 x 10(-7) and 10(-6) M were greater at 2 than 4 Hz. In the presence of veratridine at 3 x 10(-6) M, the ventricle would not pace. 4. BDF 9148 at 10(-7)-10(-5) M augmented the cardiac stimulation responses and the augmenting effects with 10(-7) and 3 x 10(-7) M were greater at 2 than 4 Hz and the effect was maximal at 3 x 10(-7) M and submaximal at 10(-5) M. The effects of BDF 9148 at 10(-5) were not readily reversible. 5. Lignocaine at 10(-4) M had no effect on the ventricular action potential duration but decreased the threshold potential and amplitude and also reduced the cardiac stimulation force responses. In the presence of lignocaine, the augmenting effects of veratridine and BDF 9148 on ventricular force were reduced. 6. In summary this study has shown that BDF 9148 prolongs the action potential and augments the contractile force responses of the rat right ventricle by a lignocaine-sensitive mechanism. BDF 9148 or similar drugs may have potential as positive inotropes in the treatment of heart failure.

Action Potentials↗

PubMed1995

The effects of racemic, (+)- and (-)-pinacidil on the membrane potential of the rat aorta.

The endothelium-intact and -denuded rat aorta is hyperpolarized by racemic and (-)-pinacidil, probably by opening ATP-dependent potassium channels. (+)-Pinacidil caused depolarization of the endothelium-intact and -denuded rat aorta. The depolarization induced by 20 mAM KCl in the endothelium-intact rat aorta was reversed by racemic and (-)-, but not by (+)-pinacidil. On the endothelium-intact rat aorta, isoprenaline produced hyperpolarization and ICI 118551 (erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol) had no effect alone but prevented isoprenaline from causing hyperpolarization. The hyperpolarization induced by isoprenaline was reversed by racemic and (+)-, but not by (-)-pinacidil. Glibenclamide depolarized the endothelium-intact rat aorta and prevented the hyperpolarizing action of racemic pinacidil and (-)-pinacidil. (+)-Pinacidil prevented the hyperpolarizing action of (-)-pinacidil. Glibenclamide is probably preventing the hyperpolarization associated with opening of the ATP-dependent potassium channel by blocking this channel. Several mechanisms may underlie the depolarizing action of (+)-pinacidil, including blocking of ATP-dependent potassium channels.

Animals↗

PubMed1994

The effects of racemic cromakalim, BRL 38226 and levcromakalim on the membrane potential of the rat aorta and of BRL 38226 on the contractile activity of the rat aorta and portal vein.

The effects of racemic cromakalim and the (+)-3R,4S and (-)-3S,4R isomers, BRL 38226 and levcromakalim respectively, on the membrane potential of the rat aorta have been determined. In addition, preliminary studies of the effects of BRL 38226 on the contractility of the rat aorta and portal vein have been made. The rat aorta is hyperpolarized by racemic cromakalim at 10 microM and by levcromakalim at 1 microM, but is depolarized by BRL 38226 at 1 microM. In the presence of depolarization with 20 microM KCl, racemic cromakalim and levcromakalim, but not BRL 38226, reversed the depolarization of the rat aorta. In the presence of hyperpolarization with isoprenaline at 1 microM or in a CaCl2-free Krebs solution, racemic cromakalim and BRL 38226, but not levcromakalim reversed the hyperpolarization. Glibenclamide at 0.3 and 1 microM depolarized the rat aorta. Pretreatment with glibenclamide at 1 microM prevented the hyperpolarizing action of racemic cromakalim but did not alter the depolarizing action of BRL 38226. Pretreatment with BRL 38226 at 10 microM also prevented the hyperpolarizing action of racemic cromakalim. Contractility studies demonstrated that BRL 38226 and glibenclamide have no effect on the resting tone of the rat aorta in normal Krebs solution. However in a CaCl2-free Krebs solution, BRL 38226 and glibenclamide, 0.1-100 microM, caused small contractions. BRL 38226 and glibenclamide increased the spontaneous contractile activity of the rat portal vein in normal Krebs solution. The present study illustrates that levcromakalim opens the ATP-dependent potassium channels of the rat aorta to cause hyperpolarization. BRL 38226 and glibenclamide produce depolarization and contraction of the rat aorta and increase the contractile activity of the rat portal vein, possibly by blocking the ATP-dependent potassium channels.

Animals↗

PubMed1992

Effects of potassium channel openers and calcium channel blockers on the force responses of the electrically driven rat right ventricle strip.

1. The effects of potassium channel openers (cromakalim and pinacidil) and of calcium channel blockers (verapamil, diltiazem and flunarizine) on the contractile responses of the rat right ventricle have been determined. 2. On the electrically driven rat right ventricle cromakalim at 3 x 10(-7), 10(-6), 3 x 10(-6) M and 10(-5) M, and pinacidil at 10(-6), 10(-5) and 3 x 10(-5) M had no effect on the force responses to cardiac stimulation or to isoprenaline. 3. Pinacidil at 10(-4) M in a vehicle of 0.7% ethanol reduced the force responses to cardiac stimulation. This inhibitory effect was solely due to the ethanol. Pinacidil in 5 x 10(-4) M HCl (which had no effect alone) potentiated some of the responses to isoprenaline. 4. Verapamil, greater than or equal to 10(-6) M, diltiazem, greater than or equal to 10(-5) M, and flunarizine, greater than or equal to 10(-6) M, reduced the force responses to cardiac stimulation and to isoprenaline. 5. The present study has shown that calcium channel blockers, but not potassium channel openers, have inhibitory effects on the rat right ventricle.

Animals↗

PubMed1989

Dose-dependent reduction by Ro 15-4513 in mice of the effects of ethanol and some other general depressant drugs.

In mice, Ro 15-4513 reduced the anaesthesia induced by ethanol and some other general depressant drugs, but was less effective against others. The order of potency was, from greatest reduction to least, ethanol, t-butanol, trichloroethanol, urethane, chlormethiazode, pentobarbitone. Of the two gaseous anaesthetics that were tested, ether anaesthesia was reduced but halothane was not. These results appeared independent of the doses of depressant or of Ro 15-4513; the effect of Ro 15-4513 in reducing ethanol anaesthesia was blocked by flumazenil (Ro 15-1788). It would appear that the benzodiazepine receptor complex is of importance in the induction of anaesthesia, most significantly with ethanol and to a diminishing degree with the other general depressants tested.

Anesthetics↗

PubMed1981