Selective additive effect of phenylephrine to the inotropic action of isoproterenol on rabbit left atria.

The chronotropic and inotropic effects of isoproterenol, adrenaline and phenylephrine were examined in isolated right and left rabbit atria. 1. Spontaneous right atrial rate (RAR) and left atrial contractile force (LACF) (electrically stimulated at 2 Hz) were monitored during separate concentration-response curves to all 3 agonists. The order of potency for both parameters was isoproterenol greater than adrenaline greater than phenylephrine. 2. At maximum agonist effect, adrenaline produced the greatest LACF increase, followed in order by isoproterenol and phenylephrine. 3. When phenylephrine (6.0 x 10(-5) M) was added to the left atria maximally stimulated with isoproterenol, an additional 32% increase in LACF was recorded, but an additive effect was not noted when phenylephrine was added to atria maximally stimulated with adrenaline. The LACF achieved by a combination of isoproterenol and phenylephrine approximated the maximum LACF induced by adrenaline alone. 4. At maximum agonist effect, isoproterenol and adrenaline produced a greater RAR increase than phenylephrine. Further, phenylephrine did not increase the maximum RAR effect of isoproterenol or adrenaline. 5. Adrenergically mediated chronotropic increases appear to be mediated by a beta adrenoceptor and the maximum response to agonists of full intrinsic activity can not be further increased by agonist combinations. However inotropic increases appear to be mediated by 2 adrenoceptor types which may be simultaneously stimulated to produce additive effects. The two adrenoceptors mediating inotropic change are probably alpha and beta.