Effects of Calcium-Antagonistic Coronary Vasodilators on Myocardial Contractility and Membrane Potentials

Nabata, Hiroyuki

doi:10.1254/jjp.27.239

Cited by 85 publications

(18 citation statements)

References 2 publications

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“…The test drugs were added 30 min before the fourth concentration-response curve for calcium was ob tained. The calcium-blocking effects of these drugs were calculated from the shift in the fourth as com pared to the third concentration-response curve for calcium and expressed in terms o f apparent pA2 val ues according to the following equation [ 10]: Values are mean ± SE from 4-12 experiments. The potency ratios are calculated on the basis of verapamil being 1.…”

Section: Methodsmentioning

confidence: 99%

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Nakagawa

Gudenzi

1986

Pharmacology

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Calcium entry blocking activities of adenosine and its potentiating compounds (dipyridamole, lidoflazine and dilazep) were studied in potassium (100 mmol/l) depolarized, dog, large coronary artery strips, in comparison to nifedipine, verapamil and diltiazem. Apparent pA₂ values were calculated by using concentration-response curves for calcium before and 30 min after the addition of each dilator drug. The order of potency (using both pA₂ and IC₅₀ values) for the calcium entry blocking effect was: nifedipine > verapamil > diltiazem > lidoflazine > dilazep. Dipyridamole and adenosine had negligible calcium entry blocking activities (about 10,000 times less potent than verapamil). The calcium entry blocking activity of verapamil (using pA₂ values) was 39.8 times less potent than nifedipine, and 3.6, 21.4 and 97.7 times more potent than diltiazem, lidoflazine and dilazep, respectively. The maximum relaxations induced by adenosine (3.7 × 10^–4 mol/l) and dipyridamole (5 × 10–⁵ mol/l) were less than 20% that of 3 × 10^–4 mol/l papaverine. However, the other test drugs caused 80–90% relaxation under similar conditions. The relaxing effect of adenosine was inhibited by 8-phenyltheophylline (adenosine receptor antagonist) and potentiated by EHNA (an adenosine deaminase inhibitor), while dilazep-induced relaxation was not affected by these drugs. These findings suggest that the calcium entry blocking effect of dilazep in dog, large coronary artery strips is not mediated through adenosine.

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Section: Methodsmentioning

confidence: 99%

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Nakagawa

Gudenzi

1986

Pharmacology

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“…This lack of effect of Na antag onists indicates that, in contrast to normotopic pacemaker activity [18], there is no major involvement ofNa ions in this model. This is important for the validity of this model in order to compare the effects of sev eral calcium entry blockers; indeed diltiazem and, to a lesser degree, verapamil possess an inhibitor effect on the Na carrier in addition to their antagonist effects on Ca ions [19],…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Nifedipine, Diltiazem and Verapamil on the Mechanical Activity of Rabbit Papillary Muscles Induced by Barium Chloride

Roy¹,

Pruneau²

1986

Pharmacology

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Isolated rabbit papillary muscles that do not present pacemaker activity under physiological conditions develop a spontaneous activity in the presence of 2 mmol/l BaCL₂. Ba-induced contractions were unaffected by high concentrations of the Na antagonist pro-cainamide (10^–5 mol/l). Tetrodotoxin (10^–5 mol/l), a specific blocker of the fast Na current, only slightly increased the amplitude of contractions. In contrast, the calcium entry blockers nifedipine, diltiazem, and verapamil strongly depressed the mechanical activity in a time- and dose-dependent manner. The concentrations that decreased the amplitude and frequency of contractions by 50% were determined. The order of potency was nifedipine >> diltiazem ≥ verapamil. Ba-induced automaticity is a particularly useful model on which the potency of calcium entry blockers could be assessed.

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“…An equilibration period of 60 min was allowed before starting experiments. The experiments were also performed using the partially depolarized left atrial preparation according to the method described previously (Nabata, 1977). Briefly, the contractions were recorded in normal Krebs-Henseleit solution as described above.…”

Section: Methodsmentioning

confidence: 99%

Positive inotropic and chronotropic effects of trypsin and some other proteolytic enzymes in the guinea‐pig heart

Imai

Kawada

Kimura

et al. 1987

British J Pharmacology

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1 In atrial preparations of the young guinea-pig (body weight 150-250 g), five proteolytic enzymes (trypsin, chymotrypsin, bacterial-Al-proteinase (nagarse), bromelain and kallikrein) produced concentration-dependent positive inotropic and chronotropic effects, while they exerted only minimal effects on the papillary muscle preparations. 2 To characterize the effects, further experiments were conducted in atrial preparations using trypsin. There was a strong tendency for tachyphylaxis: a second exposure to the same concentration of trypsin resulted in considerably smaller positive inotropic and chronotropic effects. The positive inotropic and chronotropic effects of this substance were not affected by propranolol (5 x 10-M). However, an accumulation of cyclic AMP was observed and the positive inotropic and chronotropic effects were potentiated by aminophylline (10-M) in association with an augmentation of the accumulation of cyclic AMP. In preparations partially depolarized with high K+ (22 mM) medium (contractions ceased under this condition) trypsin 100 fig ml-' reinstated the contraction. Treatment ofthe preparation with aprotinin (200 u ml1 ') resulted in a strong inhibition of the positive inotropic and chronotropic effects. 3 Islet activating protein (IAP), a specific inhibitor of the 'inhibition specific' guanine nucleotide binding regulatory protein ofthe adenylate cyclase system, did not produce significant inhibition of the positive inotropic and chronotropic effects of trypsin, whereas it produced a complete inhibition of the negative inotropic and chronotropic effects of carbachol. 4 These results suggest that the positive inotropic and chronotropic effects ofproteolytic enzymes are intimately connected with the proteolytic activities through which adenylate cyclase is activated to produce an accumulation of cyclic AMP within the myocardium. The destruction of the 'inhibition specific' guanine nucleotide regulatory protein of the adenylate cyclase was not substantiated as a mechanism of activation of the adenylate cyclase.

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Effects of Calcium-Antagonistic Coronary Vasodilators on Myocardial Contractility and Membrane Potentials

Abstract: Abstract-Toclarify the relation between the negative inotropic effects of "calcirun antagonistic" vasodilators and their calcium-antagonistic effects,

Cited by 85 publications

References 2 publications

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Comparison of the Effects of Nifedipine, Diltiazem and Verapamil on the Mechanical Activity of Rabbit Papillary Muscles Induced by Barium Chloride

Positive inotropic and chronotropic effects of trypsin and some other proteolytic enzymes in the guinea‐pig heart

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