THE USE OF THE RABBIT AORTA STRIP IN THE ANALYSIS OF THE MODE OF ACTION OF l-EPINEPHRINE ON VASCULAR SMOOTH MUSCLE

¹ Department of Pharmacology, UCLA Medical Center, Los Angeles, California

The rabbit aorta strip preparation has been developed to allow quantitative measurement of the kinetics and equilibrium characteristics of the response to l-epinephrine.

After an initial soaking of 2 hours in Krebs saline, the preparation appears to reach a steady state with its surroundings that is maintained for a minimum of a further 6 hours.

The homogeneity of strips taken from the upper and middle thirds of the aorta has been demonstrated using pharmacological and physiological criteria. This makes it legitimate to use one strip as a simultaneous control for another.

The sensitivity of the smooth muscle of this preparation is independent of tension under isotonic conditions.

Using the equilibrium height of response, the relation between prohit of contraction height and log dose is linear over a wide dose range and at all temperatures tested. Although the slope of the curve does not change with temperature, the relationship between M.E.D. and temperature is complex.

An analysis of the kinetics of contraction of the aorta to l-epinephrine has been made dependent on the basic, hut as yet unproven, assumption that the concentration of drug at the receptor site at any height during a kinetic response is the same as the equilibrium dose producing that height.

This analysis suggests that up to a dose level 2 to 3 times the M.E.D. the rate of contraction is controlled by the rate of diffusion of l-epinephrine to its receptor site. In comparison to this, the rate of reaction of the drug with its receptors is fast.

This analysis also suggests that there is a diffusion barrier between the extracellular space and the adrenergic receptors, that this barrier is activated and that the E_a of the diffusion of l-epinephrine through this barrier is 37,000 ± S.E. 1500 cal/mol/°C.