Acute cardiovascular effects of the α2-adrenoceptor antagonist, idazoxan, in rats:: Influence of the basal sympathetic tone

Intravenous administration of the alpha(2)-adrenoceptor antagonist, idazoxan, elicits variable cardiovascular effects, depending on experimental conditions. In this study, the effects of idazoxan were investigated in rats with high. low, or no basal sympathetic tone. In a group of conscious Sprague-Dawley rats (n = 9), mean arterial pressure (MAP), heart rare (HR), and renal sympathetic nervous activity (RSNA) were recorded. Idazoxan (250 mu g/kg, i.v.) induced a transient decrease in MAP (-12 +/- 3 mm Hg) that was accompanied by increases in HR (49 +/- 14 beats/min) and RSNA (53 +/- 14%). In six of nine rats, a light pentobarbitone anesthesia was given. Basal RSNA was decreased (6.0 +/- 1.3 mu V from 12.8 +/- 4.1 mu V; p < 0.05), and the depressor effect of idazoxan was reversed to a presser effect (21 +/- 6 mm Hg) associated with bradycardia (-16 +/- 8 beats/ min) and sympathoinhibition (-56 +/- 15%). In eight conscious intact rats, idazoxan (250 mu g/kg, i.v.) attenuated by similar to 40% the presser response to the selective alpha(1)-adrenoceptor agonist, cirazoline (0.5 mu g/kg, i.v.). In three groups of six to seven ganglion-blocked (chlorisondamine, 2.5 mg/kg, i.v,) conscious rats, idazoxan dose-dependently increased mean arterial pressure (MAP: 39 +/- 2, 55 +/- 3, and 69 +/- 4 mm Hg at 125, 250, and 500 mu g/kg, i.v., respectively) with minimal changes in HR. In contrast, the noradrenaline-releasing agent, tyramine (62.5, 125, and 250 mu g/kg, i.v.), dose-dependently increased both MAP and HR. The alpha(1)-adrenoceptor antagonist, prazosin (1 mg/kg, i.v.; n = 8) blunted by similar to 70% (p < 0.01) the presser effect of 250 mu g/kg idazoxan. It is concluded that in rats with high sympathetic tone, idazoxan has depressor effects, most likely related to its peripheral alpha-adrenoceptor antagonist properties. In rats with low or no sympathetic tone, idazoxan induced presser responses mainly secondary to its partial agonist activity at vascular postjunctional alpha(1)-adrenoceptors.