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 10μM) 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 (I(subscript Na)) in isolated rat ventricular and guinea pig and human atrial cells was also inhibited by prazosin (1 to 10μM) dose-dependently. Inhibition of I(subscript Na) in rat ventricular and guinea pig atrial cells by prazosin (1 to 10μM) was not associated with the left shift of the voltage- dependent steady-state inactivation curves of I(subscript Na). The time constant of recovery of I(subscript Na) from inactivation state was also unchanged. Compared with the inhibition of I(subscript Na), the transient outward current (I(subscript to)), inwardly rectifying potassium current (I(subscript KI)) and calcium inward current (I(subscript Ca)) in rat ventricular cells were unaffected by prazosin. The I(subscript to) in human atrial cells was also not affected by prazosin. It is concluded that prazosin inhibited I(subscript Na) by selective binding to open state of Na(superscript +) channels. The inhibition of I(subscript Na) is unrelated to the blockade of myocardial α1-adrenoceptors but contribute to the negative inotropic effect of prazosin.

並列關鍵字

prazosin ； alpha-adrenoceptor ； sodium current ； calcium current ； potassium current ； contractility

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