Abstract
Pretreatment of guinea pigs with α-methyldopa did not appreciably alter the effect of norepinephrine upon either the rate of isolated atria or the force of contraction of isolated left atrial strips. Pretreatment with pargyline, a monoamine oxidase inhibitor, slightly reduced the maximum response of the pacemaker to norepinephrine, but did not alter the effects of norepinephrine on force of contraction. l-α-Methyl norepinephrine was found to be equipotent with norepinephrine on both rate and force of contraction. In contrast to the effects of norepinephrine, the effects of indirectly-acting sympathomimetic amines, tyramine, d-amphetamine and mephentermine, upon isolated atria and isolated left atrial strips were enhanced by pretreatment of guinea pigs with pargyline. Pretreatment with α-methyldopa enhanced the effects of all three indirectly-acting amines upon the rate of the pacemaker but not upon the force of contraction of the isolated left atrial strip. The response of the pacemaker to accelerans nerve stimulation and of the isolated left atrial strip to field stimulation was not affected by pretreatment with either pargyline or α-methyldopa. These observations indicate that a substantial amount of the norepinephrine released by indirectly-acting sympathomimetic amines is oxidatively deaminated before leaving the nerve terminal. In addition, they are consistent with the view that the norepinephrine storage sites affected by indirectly-acting amines differ from those storage sites affected by nerve stimulation.
Footnotes
- Accepted September 7, 1965.
- The Williams & Wilkins Comapny
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