Abstract
1. The effects of α 1 adrenoceptor blocking agents doxazosin, indoramin, 5-methylurapidil, niguldipine, WB-4101 and chloroethylclonidine (CEC) on the force of contraction ( F c), velocity of contraction (+ dF/dt) and relaxation (− dF/dt) of guinea pig papillary muscles were studied. 2. All examined substances were applied in a wide concentration range (0.01–30.0 μM) for at least 30 min at each concentration. Only α 1a blockers [i.e., niguldipine (0.01–0.3 μM), 5-methylurapidil (1–30 μM) and WB-4101 (1–30 μM)] showed a concentration-dependent negative inotropic action. 3. This effect was significantly attenuated in the presence of glibenclamide (1 μM) and almost completely abolished by 1,3-dipropyl-8- p-sulfophenylxanthine (1 μM), an antagonist of adenosine receptors with a slight selectivity for the A 1 subtype. 4. Pretreatment with dibenamine, an irreversible blocker of α 1 adrenoceptors (0.6 μM for 40 min), abolished this effect, whereas pretreatment with CEC, an irreversible blocker of α 1b adrenoceptors (1 μM for 20 min), and pertussis toxin (10 μg/kg IP, 4 to 5 days before experiments) diminished it. 5. The α 1a adrenoceptor blocking agents in the presence of the unblocked α 1b adrenoceptor trigger the negative inotropic action, which seems to include adenosine receptor stimulation and activation of ATP-sensitive K + channels (K ATP) through an inhibitory G protein.
Published Version
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