Effects of acute and chronic administration of idazoxan on blood pressure and plasma catecholamine concentrations of rats

D Harland and MJ Brown

Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.

To test the hypothesis that alpha-2 adrenoceptor antagonists can modulate sympathetic nerve release of norepinephrine in vivo through blockade of peripheral prejunctional alpha-2 adrenoceptors, acute and chronic effects of the alpha-2 adrenoceptor antagonist idazoxan on mean arterial pressure (MAP), heart rate and plasma catecholamine concentrations have been investigated in conscious and anesthetized rats. In normotensive rats, a single i.v. dose of idazoxan (300 micrograms kg-1) caused an immediate 2-fold increase in plasma concentration of norepinephrine and epinephrine, a transient increase in heart rate but no significant change in MAP. Plasma norepinephrine concentration of conscious normotensive rats increased significantly during a 4-hr i.v. infusion of idazoxan (300 micrograms kg-1 hr-1) with no concomitant changes in MAP or heart rate. In anesthetized spontaneously hypertensive rats, the increases in plasma norepinephrine concentration and heart rate caused by i.v. idazoxan (300 micrograms kg- 1) were accompanied by a significant decrease in MAP. The increase in plasma norepinephrine after idazoxan in spontaneously hypertensive rats was much greater than that produced by an equihypotensive dose of the vasodilator hydralazine. Normotensive rats treated continuously for 7 days with s.c. idazoxan (7.5 mg kg-1 day-1) had similar blood pressures and plasma catecholamine concentrations to vehicle-treated rats. These results suggest that idazoxan causes a greater increase in plasma norepinephrine concentration than that which can be attributed to baroreceptor stimulation. Blockade of prejunctional alpha-2 adrenoceptors by idazoxan may, therefore, increase release of norepinephrine from peripheral sympathetic nerves of anesthetized and conscious rats. This effect is short-lived and does not influence blood pressure of normotensive rats.

Volume 245, Issue 1, pp. 265-273, 04/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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