Effects of prazosin on rat, guinea pig and human cardiac tissues.
In this study, the mechanical and electrophysiological effects of prazosin were examined in rat, guinea pig and human cardiac preparations. Prazosin (0.3 to 10 microM) inhibited the spontaneous beating rate of rat right atria and the twitch tension of driven left atria and right ventricular strips dose-dependently. Inward sodium current (INa) in isolated rat ventricular and guinea pig and human atrial cells was also inhibited by prazosin (1 to 10 microM) dose-dependently. Inhibition of INa in rat ventricular and guinea pig atrial cells by prazosin (1 to 10 microM) was not associated with the left shift of the voltage-dependent steady-state inactivation curves of INa. The time constant of recovery of INa from inactivation state was also unchanged. Compared with the inhibition of INa, the transient outward current (Ito), inwardly rectifying potassium current (IK1) and calcium inward current (ICa) in rat ventricular cells were unaffected by prazosin. The Ito in human atrial cells was also not affected by prazosin. It is concluded that prazosin inhibited INa by selective binding to open state of Na+ channels. The inhibition of INa is unrelated to the blockade of myocardial alpha 1-adrenoceptors but contribute to the negative inotropic effect of prazosin.
Su
M J
MJ
Department of Pharmacology, National Taiwan University, Taipei, R.O.C.
Chi
J F
JF
Chu
S H
SH
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D011224:Prazosin