Interactions between sympathomimetic agonists and blocking agents: cardiac effects of phenylephrine and isoproterenol

In the isolated rat atria the effects of phenylephrine (alpha-agonist) and isoproterenol (beta-agonist) on the contractile force and heart rate were studied either in presence or not of alpha- and/or beta-blockade. Phentolamine 10(-6) M and propranolol 10(-8) M were used as alpha- and beta-antagonists, respectively. The chronotropic dose-response curves were made in both spontaneously beating atria while inotropic effects were derived from left atria driven at 1 Hz, 5 msec and voltage about 20 percent above threshold. Both agonists induced an inotropic effect that could be significantly blocked by phentolamine, propranolol and both antagonists given together. The chronotropic dose-response curve of isoproterenol (pD2 = 10.70 +/- 0.11) was blocked by phentolamine (pD2 = 9.27 +/- 0.08, p less than 0.001) and propranolol (pD2 = 9.21 +/- 0.19, p less than 0.001). Contrarily, pentolamine was unable to shift to the right the chronotropic dose-response curve for phenylephrine (pD2 = 6.48 +/- 0.07 and 6.63 +/- 0.10, respectively). This action of phenylephrine on the heart rate was significantly blocked by propranolol (pD2 = 6.21 +/- 0.13, p less than 0.05) and by propranolol plus phentolamine (pD2 = 6.07 +/- 0.04, p less than 0.001). From the present results it is concluded that in the rat's atrial myocardium there exist alpha- and beta-adrenoceptors mediating the positive inotropic effect of isoproterenol and phenylephrine. Yet, the chronotropic action seems to behave in a different way: while isoproterenol triggered either type of receptors; phenylephrine is only mediated by beta-adrenoceptors.U