Effect of Clonidine on Tyrosine Hydroxylase Activity in the Adrenal Medulla and Brain of Spontaneously Hypertensive Rats

• Published in: Basic & clinical pharmacology & toxicology 2009-02, Vol.104 (2), p.113-121
• Main Authors: Moura, Eduardo, Afonso, Joana, Serrão, Maria Paula, Vieira‐Coelho, Maria Augusta
• Format: Article
• Language: English
• Subjects: Adrenal Medulla - drug effects; Adrenal Medulla - enzymology; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Agonists - therapeutic use; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blotting, Western; Brain - drug effects; Brain - enzymology; Cardiology. Vascular system; Catecholamines - blood; Catecholamines - metabolism; Clonidine - pharmacology; Clonidine - therapeutic use; Heart Rate - drug effects; Hypertension - drug therapy; Hypertension - enzymology; Hypertension - physiopathology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System - drug effects; Tyrosine 3-Monooxygenase - biosynthesis; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2008.00339.x

:  In the present study, we evaluated the effect of the α2‐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 µg/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 Vmax values and no changes in KM 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 Vmax values and no changes in KM 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 α2‐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.