Is the sympathoexcitatory effect of yohimbine determined by brain yohimbine concentration?
Plasma noradrenaline and adrenaline concentrations, plasma renin concentration (PRC), and serum and brain yohimbine concentrations were measured in conscious Sprague-Dawley rats after the s.c. and i.v. injection of yohimbine. The s.c. and i.v. administration of 1 and 3 mg/kg of yohimbine (30 min post-injection) elicited equivalent and dose-related increases in plasma noradrenaline concentration. At 30 min post-injection, the 1 mg/kg dose given s.c. or i.v. did not increase plasma adrenaline concentration or PRC, whereas the 3 mg/kg dose caused comparable increases in plasma adrenaline concentration and PRC when given s.c. or i.v. Brain yohimbine concentration increased in a dose-related manner whereas serum yohimbine concentration was not significantly different 30 min after treatment with the 1 1 and 3 mg/kg doses regardless of the route of injection. Despite the fact that serum yohimbine concentration was 5-fold greater after i.v. injection as compared to s.c. administration (1 and 3 mg/kg doses), brain yohimbine concentrations were comparable after s.c. and i.v. injection and thus not dependent on either the route of administration or serum yohimbine concentration. The fact that the s.c. and i.v. injection of yohimbine lead to comparable dose-related increases in both brain yohimbine concentrations and neuroendocrine responses suggests that increased sympathetic outflow resulted primarily from an action of yohimbine at central, rather than peripheral, alpha 2-adrenoceptors. However, the data also are consistent with a purely peripheral prejunctional action of the 1 mg/kg dose and a combined central and peripheral action of the 3 mg/kg dose.