The contractile and electrophysiological effects of rolipram in guinea-pig papillary muscles and isolated ventricular myocytes.
Isometric force, action potentials and in voltage-clamp Isi (second inward current) and its current voltage relation were recorded in papillary muscles from guinea-pigs and from guinea-pig isolated ventricular myocytes (35-37 degrees C, 0.5-1 Hz). Rolipram (1-100 microM) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose-dependent manner and at 30 microM THR was prolonged by 25.3 +/- 6% (n = 10, P < 0.001). The effect of 30 microM rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3 +/- 3.1% (n = 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8 +/- 3.3% (n = 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13 +/- 6 ms (n = 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on Isi and its current-voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
Mörner
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SE
Department of Pharmacology, University of Lund, Sweden.
Arlock
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P
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D020889:Rolipram