Acute cardiovascular effects of the alpha(2)-adrenoceptor antagonist, idazoxan, in rats: Influence of the basal sympathetic tone

Intravenous administration of the alpha(2)-adrenoceptor antagonist, idazoxa n, elicits variable cardiovascular effects, depending on experimental condi tions. In this study, the effects of idazoxan were investigated in rats wit h 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 ren al 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 acco mpanied 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 w as decreased (6.0 +/- 1.3 mu V from 12.8 +/- 4.1 mu V; p < 0.05), and the d epressor effect of idazoxan was reversed to a presser effect (21 +/- 6 mm H g) associated with bradycardia (-16 +/- 8 beats/ min) and sympathoinhibitio n (-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 o f six to seven ganglion-blocked (chlorisondamine, 2.5 mg/kg, i.v,) consciou s 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., re spectively) with minimal changes in HR. In contrast, the noradrenaline-rele asing 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 effe ct of 250 mu g/kg idazoxan. It is concluded that in rats with high sympathe tic tone, idazoxan has depressor effects, most likely related to its periph eral alpha-adrenoceptor antagonist properties. In rats with low or no sympa thetic tone, idazoxan induced presser responses mainly secondary to its par tial agonist activity at vascular postjunctional alpha(1)-adrenoceptors.