ON THE MECHANISM OF ACTION OF PHENYLEPHRINE IN RAT ATRIAL HEART-MUSCLE

Both in rat left atrial heart and in aortic smooth muscle preparations , phenylephrine (PE) caused a concentration-dependent increase in forc e of contraction (Fc) in the presence of atenolol (10 mu mol/l), which was antagonized by phentolamine, prazosin and WB 4101 in a competitiv e manner. The pA(2) values of the antagonists in the cardiac tissue we re 10-20fold lower than those in the rat thoracic aorta. In the sponta neously beating right atrium, PE exerted a positive chronotropic actio n, which was not significantly antagonized by phentolamine or prazosin . It is therefore assumed that the effects of phenylephrine in the lef t atrium and in the aorta are mediated by different subtypes of alpha( 1)-adrenoceptors, whereas the effects in the sino-atrial node are prob ably unrelated to alpha(1)-adrenoceptors. To further elucidate the mec hanisms of the positive inotropic effect of PE, action potential confi guration and Ca-45(2+) fluxes were monitored in the rat left atrium. T he increase in F-c by PE was associated with an increase in action pot ential duration (APD) and a reduction in resting membrane potential (R P). In the presence of (-)-devapamil (D888), the effects of PE on APD and RP persisted, whereas the increase in Fe was antagonized in a non- competitive manner. Forskolin (300 nmol/l) enhanced the positive inotr opic effect of PE. PE exerted a significant increase in (45)CA(2+) upt ake in beating preparations, which was abolished in the presence of (- )D888 (1 mu mol/l). In addition to the PE-induced increase in Ca-45(2) uptake, a decrease in Ca-45(2+) efflux was observed. Similarly, depo larization of the membrane by raising [K+](o) to 85 mmol/l revealed an increase in Ca-45(2+) uptake and a decrease in Ca-45(2+) efflux . The latter observations support the view that the membrane potential stro ngly determines the movement of Ca-45(2+) across the membrane. It is a ssumed that the alpha(1)-adrenoceptor-mediated changes in APD and RP m ay enhance F-c, first, by increasing net Ca2+ entry from the extracell ular space through voltage-dependent Ca2+ channels and, second, by dec reasing Ca2+ efflux possibly via the Na+/Ca2+ exchange mechanism.