Comparison of effects of a new dihydropyridine, Bay K 8644, and nifedipine on spontaneous mechanical activity in rat portal vein

Mikkelsen, E.

doi:10.1111/j.1476-5381.1985.tb08872.x

Cited by 23 publications

(16 citation statements)

References 4 publications

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“…In the presence of 0.1 ,uM nifedipine, the spontaneous activity recovered and, moreover, enhanced by 0.1 AM Bay K 8644 to about 200% of the initial level (triangles). This confirmed the preceding observation shown by Mikkelsen (11). Even after Bay K 8644 was withdrawn together with nifedipine, the total contraction was maintained at a level higher than the control (see Fig.…”

Section: Resultssupporting

confidence: 79%

“…The present results support the preceding suggestion that the spontaneous activity of portal vein, as well as the high K+-induced contraction in aorta, is quite useful for assay ing a Ca antagonist (11,14). It is well established that each twitch contraction occurs as a consequence of a short burst of spontaneous action potentials (15,16), which are susceptible to Ca-antagonists (14).…”

Section: Discussionsupporting

confidence: 80%

“…It has also been reported that benidipine selectively and competitively binds to 3H-nitrendipine binding sites of rat cardiac membranes with high affinity (21). Bay K 8644, a dihydro pyridine Ca agonist, displaces or inhibits the specific binding of 3H-nitrendipine in car diac tissues (22,23) and well-antagonizes the blockade by nifedipine in the portal vein (11). In the present study, it was additionally observed that the effect of Bay K 8644 remained predominantly after the concomi tant withdrawal of nifedipine and Bay K 8644 in the portal vein.…”

Section: Discussionsupporting

confidence: 63%

“…Therefore, it was examined whether a Ca-agonist, Bay K 8644, could antagonize the inhibition by benidipine (11 ) or accelerate the recovery from the blockade.…”

Section: Resultsmentioning

confidence: 99%

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Slow onset of and recovery from Ca blocking action of benidipine in rat aorta and portal vein.

et al. 1989

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Abstract-Effects of benidipine, a newly developed 1,4-dihydropyridine derivative, on the high K+-induced contraction in aorta and the spontaneous contraction in portal vein of the rat were examined. When either tissue was treated with a low concentration (0.1-10 nM) of benidipine for 90, 180 min or a longer period, the evoked or spontaneous contraction was reduced in a time and concentration dependent manner. The time required for 50% inhibition by 1 nM benidipine was approximately 60 and 120 min in the portal vein and aorta, respectively. Although the exact IC50 of benidipine was not determined because of the unexpectedly slow onset of the effect, it might have been overestimated previously and is apparently lower than 1 nM. After the withdrawal of 1 nM benidipine, its inhibitory action was not removed significantly even by washing for 5 hr. A partial or full recovery from the inhibition was observed in tissues pretreated with 0.3 nM benidipine. The persistent inhibition after withdrawal of 1 nM benidipine was not removed by Bay K 8644 treatment. The results strongly suggest that the slow recovery from the benidipine-induced inhibition is, at least in part, responsible for the long-lasting antihypertensive effects of benidipine.

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Section: Resultssupporting

confidence: 79%

Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 63%

“…Therefore, it was examined whether a Ca-agonist, Bay K 8644, could antagonize the inhibition by benidipine (11 ) or accelerate the recovery from the blockade.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Slow onset of and recovery from Ca blocking action of benidipine in rat aorta and portal vein.

et al. 1989

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“…For example, in isolated heart preparations high doses of Bay K 8644 produced a negative inotropic effect (Schramm et al, 1983a;Franckowiak et al, 1985). Likewise, in isolated blood vessels Bay K 8644 exhibited a biphasic effect on the contractile force (Dube et al, 1985;Mikkelsen, 1985). Franckowiak et al (1985) have demonstrated that the (-)-enantiomer of Bay K 8644 possesses vasoconstrictor and positive inotropic effects whereas high concentrations of its antipode produce negative inotropic and vasodilator effects.…”

Section: Discussionmentioning

confidence: 99%

Bay K 8644‐induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs

Abraham

Amitai

et al. 1987

British J Pharmacology

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1 The effects of intracarotid administration of Bay K 8644 on the ECG pattern along with their reversal by antianginal drugs were investigated in anaesthetized rats. 2 Intracarotid injections of Bay K 8644(0.5-50.0 tgkg-') produced a dose-related transient increase in systemic blood pressure.3 The pressor response was accompanied by ST segment elevation (0.5-l0.0jgkg-'), ST segment depression concomitant with the occurrence of arrhythmias (20.0 figkg-'), or A-V block (50.0 ftgkg-').4 ST segment elevation reached its maximal value within 15 s and could be observed for 30-240 s. 5 The increase in blood pressure was immediate (within 5 s) and short lasting (30-120 s). After the initial increase it returned to control levels (0.5-20.0 gkg-') or dropped below (50.0ftgkg-').6 The ST segment elevation caused by 5.0 ggkg-' Bay K 8644 (submaximal dose) was blocked by antianginal drugs (e.g. nitroglycerin, nifedipine and diltiazem) and by the peripheral benzodiazepine receptor antagonist PK 11195. However, the pressor response was not blocked by any of the drugs used. 7 ST segment elevation (or depression) induced by intracarotid administration of Bay K 8644 provides a useful tool for the evaluation of potential antianginal drugs.

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Effects of sodium vanadate on the smooth muscle of the rat portal vein

Shimamura

Sunano

1988

Naunyn-Schmiedeberg's Arch Pharmacol

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The effects of vanadate on the mechanical and electrical activity of the rat portal vein were examined. Vanadate increased the height of the spontaneous contractions of the portal vein without affecting basal tension. This effect was not blocked by alpha-blockers or atropine. Vanadate did not exert any effect when the spontaneous contractions were abolished by high concentrations of verapamil or in the absence of Ca. Vanadate did not change the resting membrane potential of the smooth muscle cells of the vein, but it increased the rate of rise and the amplitude of the action potentials and the number of action potentials per burst. The intracellular Na content was increased slightly by vanadate. However, the effects of Na,K-pump inhibition by ouabain or K-removal were quite different from those of vanadate, and these procedures did not block the effect of vanadate, although they attenuated it. Vanadate also potentiated the K-contracture of the portal vein. These results indicate that vanadate increases the amplitude of the spontaneous contractions through an increase in the number of action potentials per burst which underly the contraction. These effects are not mediated by intrinsic nerve excitation or inhibition of Na,K pump activity. The facilitation of Ca entry through the voltage dependent Ca channel may be the main cause of the effect of vanadate on mechanical activity.

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Comparison of effects of a new dihydropyridine, Bay K 8644, and nifedipine on spontaneous mechanical activity in rat portal vein

Cited by 23 publications

References 4 publications

Slow onset of and recovery from Ca blocking action of benidipine in rat aorta and portal vein.

Slow onset of and recovery from Ca blocking action of benidipine in rat aorta and portal vein.

Bay K 8644‐induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs

Effects of sodium vanadate on the smooth muscle of the rat portal vein

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