Effects of the ACE inhibitor, perindoprilat, and of angiotensin II on the transient inward current of guinea pig ventricular myocytes.
Hypothetically, certain ischemic and reperfusion arrhythmias may result from the activity of the calcium-dependent transient inward current. The effects of the angiotensin converting enzyme inhibitor, perindoprilat, on the transient inward current of guinea pig ventricular myocytes were studied. The transient inward current was evoked by superfusing the cell with a modified Tyrode's solution (5.4 mM CaCl2 and 0.54 mM KCl). Repetitive voltage clamp steps from a holding potential of -55 to +20 mV (1,000 ms, 0.1 Hz) were applied while dialyzing the cell internally. When administered simultaneously with the change over to the low K+ high Ca2+ solution, perindoprilat (1 microM) decreased the transient inward current from -9.55 +/- 0.31 to -3.24 +/- 0.24 microA/cm2 (p less than 0.05). A similar decrease was observed when perindoprilat was administered after first inducing the transient inward current. Perindoprilat also protected from the effects of norepinephrine (0.01 and 0.1 microM), which increased the amplitude of the transient inward current from -9.76 +/- 0.17 and -9.99 +/- 0.32 microA/cm2 at the end of the 15-min control period to -11.13 +/- 0.67 and -12.67 +/- 0.49 microA/cm2, respectively (p less than 0.05). The effects of perindoprilat were independent of angiotensin II, which in this preparation decreased the transient inward current. Based on our results, we conclude that perindoprilat decreases the transient inward current and prevents the action of norepinephrine on the transient inward current. The direct effect of the angiotensin converting enzyme inhibitor observed on the transient inward current might explain why angiotensin converting enzyme inhibitors reduce calcium-dependent ouabain-induced or reperfusion arrhythmias.
Enous
R
R
Department of Medicine, Medical School, University of Cape Town, Republic of South Africa.
Coetzee
W A
WA
Opie
L H
LH
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D015220:Calcium Channels; D007211:Indoles; D007473:Ion Channels; D000804:Angiotensin II; C053500:perindoprilat; D010042:Ouabain; D009638:Norepinephrine