Premium
Interaction between sympathomimetic amines, ephedrine, tyramine and norepinephrine at uptake 1 in sympathetic nerves and the role of nitric oxide
Author(s) -
Simaan Joseph A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.959.1
Subject(s) - tyramine , chemistry , ephedrine , nitric oxide , agonist , norepinephrine , receptor , atropine , endocrinology , blockade , medicine , pharmacology , biochemistry , dopamine , organic chemistry
Ephedrine (E) is alpha and beta adrenoceptor sympathomimetic agonist that acts partly directly on receptors and partly by liberating norepinephrine (NE) from vesicular stores. Repeated administration leads to tolerance. Since E enters uptake 1 in sympathetic nerve terminals to liberate NE, its interaction with tyramine (T) indirect‐ acting and NE direct‐ acting sympathomimetics and the role of nitric oxide (NO) in E tolerance and this interaction, were explored in anesthetized rats. Repeated single doses of E (2 mg/kg) produced tolerance in mean blood pressure from 28+/−4 to 3+/−1 mmHg after 9+/−0.8 doses (cumulative 18.1+/−1.8 mg/kg). Blockade of the synthesis of NO with nitro‐L‐arginine (NA15mg/kg) and restoration of the induced rise in pressure to control with an infusion of nitroglycerin (NG), a NO donor, partly reversed the tolerance by 8+/−1 mmHg, (285+/−62%). Tyramine (T 0.025– 0.2 mg) but not NE (0.05–0.2 ug) given before and after E tolerance, exhibited cross tolerance of 84–89% and partial recovery after NA and NG by 109–386 %. It is concluded that E enters uptake 1 to release NE and with repeated doses blocks its own entry and that of T, a process partly dependent on fresh synthesis of NO. The rest of tolerance could be due to retention of E by uptake 1 and not due to changes in receptors and post‐ receptor pathways since the effect of NE was preserved. Supported by the American University of Beirut.