The positive inotropic action of the nifedipine analogue, Bay K 8644, in guinea‐pig and rat isolated cardiac preparations

1 The biphasic positive inotropic effect of ouabain has been studied in rat ventricular strips in the presence of ethylisopropylamiloride (EIPA) an inhibitor of Na+/H+ exchange.2 EIPA (10-20IpM) depressed dose-dependently the high affinity component of the ouabain inotropic effect, whereas it did not significantly modify the low affinity inotropic effect related to high concentrations of ouabain. 3 At the EIPA concentrations studied, there was no observable modification of the inotropic effect of Bay K 8644 (IO nM, 0.3 pM) or of isoprenaline (10 nM, 1 pM). 4 These results indicate that the inotropic effect of ouabain resulting from its interaction with high affinity sites is selectively sensitive to EIPA.

Section: Resultsmentioning

confidence: 99%

Selective inhibition by ethylisopropylamiloride of the positive inotropic effect evoked by low concentrations of ouabain in rat isolated ventricles

Finet

Godfraind

1986

“…This finding is in agreement with the observation made by Vaghy. et al (1984) that Bay K 8644 and nitrendipine share the same binding sites and with the studies of Schramm et al (1983b), Yamamoto et al (1984), Spedding & Berg (1984), Kanmura et al (1984), Spedding (1985) and Finet et al (1985) which demonstrated a reversible antagonism between Bay K 8644 and other dihydropyridines (nifedipine, nisoldipine, dazopidine) on different preparations.…”

Section: Discussionmentioning

confidence: 87%

“…Finally, in our experiments on the guinea-pig trachea and on the human bronchus, as in those performed on the rabbit aorta (Schramm et al, 1983a,b;Yamamoto et al, 1984), on the guinea-pig caecum (Spedding & Berg, 1984) and on the isolated heart of dog (Vaghy et al, 1984), guinea-pig (Schramm et al, 1983,b;Finet et al, 1985) or rat (Finet et al, 1985) Bay K 8644 exerted a contractile effect in a K+-enriched medium. This effect was competitively inhibited by nicardipine, a dihydropyridine derivative.…”

Section: Discussionmentioning

confidence: 96%

Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea‐pig isolated trachea

Advenier¹,

Naline²,

Renier³

1986

1 The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potentialoperated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca2" on human isolated bronchial strips and the results were compared to those obtained on guinea-pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K+-enriched medium and in the presence of Ca2" 0.03 mM were investigated.2 In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC50 of acetylcholine or histamine on the human bronchus, but in concentrations of 10-7-10-6M it potentiated the effects of KC1 on that preparation. It did not modify the EC50 of acetylcholine, histamine or KCl on the guinea-pig trachea. 3 In Ca2+-free Krebs medium with additional K+ (30 mM), Ca2+ concentration-response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 ± 0.1 1 and 0.72 ± 0.16 log units respectively with Bay K 8644 10-8 and 10-7 M on human bronchus (n = 4) and 0.67 ± 0.16 and 1.06 ± 0.19 log units respectively with Bay K 8644 10-7 and 10-6 M on the guinea-pig trachea (n = 5).4 In Krebs medium with Ca2`0.03 mM and K+ 30 mM, Bay K 8644 (10-8 to 10-6 M) contracted both the human bronchus and the guinea-pig isolated trachea. This effect was competitively antagonized by nicardipine. 5These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca2+ influx through potential-operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea-pig isolated trachea to Bay K 8644.

“…It has been demonstrated in several studies that dihydropyridine Ca2" channel activators (Bay K 8644, CGP28392, the (+)-isomer of 202-791) increase depolarization-induced uptake of45Ca2' and release of [3H]-noradrenaline, increase the V.. of the slow response action potential and enhance myocardial contractility and calcium current (Schramm et al, 1983;Erne et al, 1984;Thomas et al, 1984;1985;Renaud et al, 1984;Brown et al, 1984;Hess et al, 1984;Finet & Godfraind, 1985;Kongsamut et al, 1985;Dube et al, 1985;Schramm & Towart, 1985). The present experiments were undertaken to determine whether stimulation of transmembrane Ca2+-entry by the light-stable activator, CGP 28392 (CGP) (Truog et al, 1984) could affect the anomalous forcefrequency relationship in rat myocardium (Langer, 1978), since it is thought that the phenomenon may be causally related to the deficiency of transmembrane Ca2" influx in this species (Nawrath, 1980).…”

Section: Introductionmentioning

confidence: 99%

Biphasic inotropic effects of a Ca²⁺ channel activator CGP28392 in rat myocardium: possible relation to intracellular Ca²⁺ release

Kobrinsky¹,

Saxon²

1987

1 The inotropic effect of a Ca2+-entry stimulator, CGP28392, (CGP) was compared in rat and frog myocardium in a concentration-and time-dependent manner. 2 Frog preparations exhibited a persistent positive inotropic effect following prolonged treatment with CGP. 3 Compared to amphibian myocardium, rat ventricular muscle exhibited a biphasic time-dependent response to CGP: an initial increase in the twitch tension amplitude of 30% was changed to a reduction of 80% below the control level during prolonged exposure to CGP (stimulation frequency, 0.2 Hz). 4 Following prolonged incubation with CGP, the resting-state contraction was decreased and the negative force-frequency relation was converted into a positive one in rat muscle. 5 Since sarcoplasmic reticulum (SR) is the major source of Ca2" in a rested-state contraction, inhibition by CGP suggests an additional, intracellular action of the Ca2" channel activator on SRCa2' release in rat myocardium.