Effect of guanfacine on kidney, heart and GABA level in DOCA and salt hypertensive rats

ABSTRACT

Experimental hypertension, was induced in rats by intramuscular injection of desoxycorticosterone [DOCA] in a dose of 50 mg/kg body weight/week for six weeks, in addition to salt in drinking water. Guanfacine was given to normotensive and hypertensive rats intraperitoneally in a daily dose of 0.09 and 0.18 mg/kg body weight for 30 days. Induction. of hypertension resulted in significant reduction in the neurotransmitter gamma aminobutyric acid [GABA] concentration in the brain, hypertrophy of the cardiac muscle and nephrosclerosis with impaired renal function. However, these histophathological and biochemical changes were paradoxically decreased after giving guarifacine in a daily dose of 0.09 mg/kg body weight for 30 days, as a result of marked decrease of blood pressure. The hypertensive rats treated with 0.18 mg/kg body weight of guanfacine for 30 days showed marked increase in the incidence and severity of cardiac and renal histopathological changes, due to the combined toxic effect of guanfacine and hypertension. The increased GABA concentration in the brain and the reduction in blood pressure after giving the drug were more significant with the low dose. In normotensive groups, rats treated with guanfacine in a daily dose of 0.18mg/kg body weight for 30 days showed moderate renal toxicity, while no biochemical or histopathological changes were observed with 0.09 mg/kg body weight of guanfacine. The two doses of guanfacine induced insignificant changes in both blood pressure and GABA concentration in the brain as compared to control non-treatment rats. Thuse law dose of guanfacine is considered more effective and safe and so it is superior to high dose in the ambulatory treatment of hypertension