Abstract

In 1966, Hudgins and Fleming (J. Pharmacol. Exp. Ther. 153: 70-80, 1966) reported that aortic strips from rabbits pretreated with reserpine exhibit what they term a "relatively nonspecific supersensitivity," i.e., the strips are supersensitive to l-norepinephrine, acetylcholine and KCl but not to histamine, 5-hydroxytryptamine and angiotensin amide. The present report is an attempt to further delineate the mechanism of this type of supersensitivity. Strips of intima-media from control and reserpine-pretreated animals were prepared by the method of Maxwell et al. (J. Pharmacol. Exp. Ther. 161: 34-39, 1968). Strips from pretreated animals were supersensitive to phenylephrine, acetylcholine and KCl but not to histamine. The dissociation constant (K_B) of phentolamine was determined and found to be the same in normal and supersensitive strips. The efficacy (e) but not the dissociation constant (K_A) of phenylephrine was changed in the supersensitive state. The maximum response to acetylcholine was increased in strips from reserpine-pretreated animals; the maximum response to phenylephrine was unaffected. In addition, reserpine pretreatment produced an increase in the sensitivity of whole aortic strips to Ba⁺⁺. These results are interpreted to indicate that this type of supersensitivity is not the result of a presynaptic change or qualitative differences in drug receptors but is the result of either quantitative changes in receptors or, as proposed by Hudgins and Fleming (1966), a change beyond the level of the drug receptor, i.e., in the physiology of the smooth muscle.