The effects of α₁-adrenergic stimulation on membrane potential, intracellular sodium activity (a_N^i_a), and contractility were investigated in the isolated papillary muscle of euthyroid, hyperthyroid, and hypothyroid guinea pigs. Cardiac alterations in the thyroid state have been shown to induce marked changes in action potential characteristics, the most pronounced shortening of action potential duration by hyperthyroidism and an increase in duration by hypothyroidism. 10^(-5) M Phenylephrine produced a decrease in a_N^i_a a in euthyroid and hypothyroid preparations, but an increase in a_N^i_a in hyperthyroid ones. The major findings were that phenylephrine produced a stronger positive inotropic effect(PIE) without initial negative inotropic effect(NIE) in hyperthyroid preparations, while phenylephrine produced markedly NIE in hypothyroid ones. The alterations in membrane potential, a_N^i_a, and contractility were abolished by 3×10^(-5)M prazosin in hypothyroidism. In hypothyroid ventricular muscle, the decrease in a_N^i_a caused by phenylephrine were not abolished or reduced by 10-5 M strophanthidin, 10^-5 M TTX, 3×10^(-4)M lidocaine, or 10^(-5)M verapamil. These results indicate that the α₁-adrenoceptor-mediated decrease in a_N^i_a is not associated with a stimulation of the Na^+ -K^+ pump, inhibition of the Na^+ or Ca^(2+) channel in hypothyroid ventricular muscle. 10^(-5)M Phenylephrine decreased a_N^i_a but increased a_N^i_a in the presence of a PKC activator phorbol dibutyrate(PDB_u).
In conclusion, it is suggested that the following sequence of events in response to phenyleplhane occur in guinea pig ventricular muscle. First, changes in thyroid state may contribute to the ventacular electrophysiological propeties or ion transport system. Second, the adrenoceptor-mediated initial transient NIE may be associated with the decrease in a_N^i_a by PKC activation.
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