Ultraviolet light‐induced photorelaxation of agonist‐contracted rabbit aorta: Further characterization and the estimation of drug‐receptor rate constants

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Abstract
Isolated strips of rabbit thoracic aorta, contracted to a steady‐state isometric tension by measured doses of α‐adrenoceptor agonists, exhibit a transient loss in tension when exposed to a flash of ultraviolet light. This response consists of an initial decrease in tension followed by a spontaneous restoration to equilibrium tension. The time course of the return to equilibrium from maximum relaxation is a biphasic exponential, resolvable into a fast phase and a slow phase. Previous work has shown that the fast phase of recovery is drug‐independent, but that the slow phase of recovery is drug‐dependent; i.e., the rate of return to equilibrium tension is unique for each agonist used to produce the initial contraction. When a system in equilibrium is perturbed in a manner such as this, the return to equilibrium is characterized by a time constant that is a function of the drug concentration. A plot of this time constant against drug consentration yields a straight line of slope and y‐intercept equal to the forward and reverse rate constants, respectively, of the chemical reaction. In this study, equilibrium perturbation by UV light was used to determine the forward and reverse rate constants (k1 and k2) of the drug‐receptor interaction and the dissociation constants (KA = k2/k1) of each of three α‐adrenoceptor agonists, norepinephrine, phenylephrine, and methoxamine. The values of KA reported here for all three agents and for different degrees of passive stretch (0.25‐g and 10‐g preload for norepinephrine, 10‐g preload for phenylephrine and methoxamine) are not significantly different from the corresponding values reported using the method of partial irreversible blockade of receptors. These findings are compatible with the hypothesis that the radiation disrupts the drug‐receptor equilibrium. Regardless of mechanism, however, the photorelaxation phenomenon may provide an additional tool for classifying vasoactive compounds.

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