Multiple effects of BAY K 8644 and nifedipine on isolated diaphragmatic fibers in vitro

Author:

Viires N.1,Pavlovic D.1,Aubier M.1

Affiliation:

1. Laboratoire de Pathologie Experimentale, Institut National de la Sante et de la Recherche, Medicale U 226, Faculte Xavier Bichat, Paris, France.

Abstract

The dose-response effects of BAY K 8644 and nifedipine on diaphragmatic contractility were assessed in vitro. Isolated diaphragmatic fibers were obtained from rats and placed in an open-topped channel of a Plexiglas tissue chamber perfused with continuously flowing Krebs solution heated to 37 degrees C. Isometric twitch force, generated in response to 1-Hz supramaximal electrical stimulation (4 times/min), was measured with a highly sensitive photoelectric force transducer. Low doses of BAY K 8644 or nifedipine (10(-7) M) were without effect on twitch tension. For 10(-6) M, twitch tension increased by 10 +/- 1% (P less than 0.005) for both drugs. For 10(-5) M, twitch tension increased by 12 +/- 1% (P less than 0.05), and maximal contractures were observed (BAY K 8644 and nifedipine). Simultaneous drug administration did not reveal mutual antagonism as expected; instead the effects were additive, with twitch tension increasing by 30 +/- 2% (P less than 0.001) for 10(-5) M BAY K 8644 + nifedipine. Both BAY K 8644 and nifedipine altered twitch characteristics. In low-calcium media (0.5 mM) twitch potentiation produced by the two drugs was further enhanced (increasing 60% for 10(-5) M BAY K 8644 or nifedipine). Contractures, by contrast, were abolished. From these results it is difficult to reconcile a unique action of these drugs on calcium channels as is conventionally accepted.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Role of Nitric Oxide on Diaphragmatic Contractile Failure in Escherichia coli Endotoxemic Rats;Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology;1998-01

2. Frequency-dependent effects of bay K 8644 on tetanic contractions of frog skeletal muscle;General Pharmacology: The Vascular System;1997-01

3. Sarcomere relaxation in hamster diaphragm muscle;Journal of Applied Physiology;1996-08-01

4. cAMP-dependent modulation of L-type calcium currents in mouse diaphragmatic cells;Respiration Physiology;1996-04

5. Effect of the calcium channel agonist Bay K8644 on mechanical and electrical responses of frog skeletal muscle;Canadian Journal of Physiology and Pharmacology;1994-10-01

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