Evidence for a peripheral component in the sympatholytic effect of clonidine in rats

Open Access
Publisher Website
Google Scholar
Abstract
1 In an attempt to assess separately the peripheral and central effects of clonidine on cardiovascular parameters and plasma catecholamine levels, the selective α2-adrenoceptor antagonist idazoxan (RX 781094) was given either intravenously (i.v.) or intracerebroventricularly (i.c.v.) to anaesthetized rats before administration of intravenous clonidine. Plasma noradrenaline and plasma growth hormone concentrations were used as indices of peripheral sympathetic nervous activity and central α-adrenoceptor stimulation, respectively. 2 Peripheral and central administration of idazoxan antagonized the cardiovascular responses to i.v. Clonidine, 5 μg kg−1. However, idazoxan was more effective against the hypotension than the bradycardia induced by clonidine. 3 Idazoxan 300 μg kg−1 i.v. and 50 μg i.c.v. prevented clonidine-induced falls in plasma noradrenaline and adrenaline. The results suggest that 50 μg idazoxan i.c.v. caused some blockade of peripheral as well as central α2-adrenoceptors. Idazoxan, 10 μg i.c.v., caused similar inhibition of the hypotensive response to clonidine as 300 μg kg−1 i.v. and 50 μg i.c.v. but did not significantly inhibit the clonidine-induced fall in plasma noradrenaline concentration. 4 Animals pretreated with i.v. or i.c.v. idazoxan had significantly lower levels of plasma growth hormone than vehicle-treated rats. Idazoxan 10 μg and 50 μg i.c.v. suppressed growth hormone secretion to the same extent. 5 These results suggest that stimulation of peripheral, prejunctional α2-adrenoceptors in anaesthetized rats may contribute to the fall in plasma catecholamines produced by i.v. clonidine, and confirm that the hypotensive effect is centrally mediated.