Vascular smooth muscle tone is modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances (e.g., epinephrine) acting on smooth muscle, simultaneously activate alpha-adrenergic receptors (alpha-AR) eliciting contraction and beta-adrenergic receptors (beta-AR) which relax the muscle. This study characterizes the beta-adrenergic response in the isolated rabbit aorta precontracted with phenylephrine (PE) or serotonin (5-hydroxytryptamine [5-HT]). The beta-adrenergic agonist isoproterenol (ISO) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension identified as desensitization. An exploratory kinetic model that describes both relaxation and desensitization as first order processes provides a good description of the experimental data. The five parameters used to describe the ISO response are: the observed rate constants for relaxation and desensitization (krel and kdes), the fractional magnitudes of the changes in tension for the two processes (R/C) and D/R), and the observed delay in the onset of the desensitization response, td. The krel and R/C were dependent on concentration of ISO in a saturable manner in rings precontracted with either 1 mumol/L PE or 1 mumol/L 5-HT and inversely related to the concentration of the contractile agonist. Yet, although the degree of fractional relaxation in the presence of PE covered the full range, that of 5-HT extended over a range of 20%. This behavior leads to the conclusion that the functional interaction between the contractile and relaxing stimuli is non additive. No dependence on the concentration of ISO was observed for D/R, kdes, and td.(ABSTRACT TRUNCATED AT 250 WORDS)