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Basic Clin Pharmacol Toxicol. 2009 Feb;104(2):113-21. doi: 10.1111/j.1742-7843.2008.00339.x. Epub 2008 Dec 5.

Effect of clonidine on tyrosine hydroxylase activity in the adrenal medulla and brain of spontaneously hypertensive rats.

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1
Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.

Abstract

In the present study, we evaluated the effect of the alpha(2)-adrenoceptor agonist clonidine on tyrosine hydroxylase activity in adrenal medulla and brain of spontaneously hypertensive rats and Wistar Kyoto rats. Six-week-old animals were treated with clonidine (100 microg/kg body weight, daily, i.p.) for 4 weeks. Treatment with clonidine significantly reduced mean arterial blood pressure in spontaneously hypertensive rats to values similar to normotensive Wistar Kyoto rats. In the adrenal medulla of spontaneously hypertensive rats, clonidine treatment produced a significant increase in tyrosine hydroxylase activity with higher V(max) values and no changes in K(M) values. This effect was accompanied by a significant increase in tyrosine hydroxylase protein expression and of noradrenaline and adrenaline levels. In the brain of spontaneously hypertensive rats, treatment with clonidine produced a significant decrease in tyrosine hydroxylase activity with lower V(max) values and no changes in K(M) values accompanied by a significant decrease in tyrosine hydroxylase protein expression and of dopamine and noradrenaline levels. In Wistar Kyoto rats, clonidine treatment had no effect on tyrosine hydroxylase activity and protein expression or catecholamine levels in adrenal medulla or brain. Clonidine treatment significantly reduced noradrenaline and adrenaline plasma levels in spontaneously hypertensive rats and Wistar Kyoto rats. In conclusion, treatment with the alpha(2)-adrenoceptor agonist clonidine prevented the increase in mean arterial blood pressure in young spontaneously hypertensive rats. This effect was accompanied by opposite effects on tyrosine hydroxylase activity in spontaneously hypertensive rat adrenal medulla and brain: an increase in adrenal medulla and a decrease in brain, bringing sympathetic function to a similar profile found in normotensive Wistar Kyoto rats.

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