Involvement of central noradrenergic mechanisms in the rebound hypertension following clonidine withdrawal.
The present study was designed to investigate the role of the central nervous system in the rebound hypertension precipitated by abrupt cessation of chronic clonidine (Cl) treatment. Male Wistar rats were treated with Cl (100 micrograms/kg, s.c.) twice daily for 7 days. Systolic blood pressure and heart rate were measured at different time intervals during Cl treatment. Rebound hypertension occurred 16-18 h after the last injection of Cl, but not in control animals given saline (0.1 ml) twice a day for 7 days. Rats were anesthetized with ether during this rebound phase of Cl withdrawal, an electrode inserted into the posterior hypothalamus, and a cannula introduced into the lateral cerebral ventricle. The posterior hypothalamus was electrically stimulated, and voltage-response curves obtained for control and Cl-treated rats revealed that the pressor responsiveness to hypothalamic stimulation was significantly potentiated in the Cl-treated rats. In addition, the depressor response to a single injection of Cl (10 micrograms) into the lateral cerebral ventricle was significantly attenuated in the Cl-treated rats. Additional experiments were performed in pithed rats to determine the involvement of peripheral adrenergic mechanisms in the rebound hypertension. When rats were pithed during the hypertensive phase of withdrawal, the blood pressure of treated rats decreased to a level which was similar to that of control animals. While the pressor responses to total spinal stimulation were similar in both the groups, the effect of exogenous norepinephrine was significantly attenuated in Cl-treated rats., These results suggest that a hyperresponsiveness of central noradrenergic pressor pathways contributes to the rebound hypertension noted following the abrupt cessation of clonidine treatment.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D003000:Clonidine; D009638:Norepinephrine