Changes in the adrenergic reactivity of spontaneously hypertensive rats after abrupt withdrawal of chronic clonidine treatment.
An experimental model of the "withdrawal syndrome" in chronic clonidine treatment is reproduced in spontaneously hypertensive rats (SHR). Medication is withdrawn abruptly after daily oral administration of 100 micrograms/kg clonidine for 12 days or after it has been received with the drinking water in a dose of approximately 250 micrograms/kg daily for 14 days. In the course of the treatment, as well as on the 24th and 48th hour after withdrawal, studies are carried out of the changes in the arterial pressure, heart rate, vascular resistance, the contractions of electrically stimulated m.anococcygeus and vas deferens, as well as some biochemical parameters (noradrenaline content in the brain and myocardium, the level of glucose and free fatty acids in the blood, the activity of phosphorylase "a" in the myocardium). In the course of clonidine treatment there is potentiation of the peripheral noradrenaline effects on the arterial pressure and vascular resistance, increasing hyperglycaemia, reduced noradrenaline content in the brain and myocardium, as well as potentiation of the inhibitory effect of clonidine on the contractions of electrically stimulated m.anococcygeus, as well as potentiation of the isoprenaline responses on the arterial pressure. The isoprenaline effects on electrically stimulated vas deferens, as well as the activity of the stimulated phosphorylase "a", decrease. No sharp increase in the arterial blood pressure was observed upon withdrawal of the clonidine treatment. The reactivity of the peripheral pre- and postsynaptic alpha-adrenergic receptors is intensified (the effects of noradrenaline on the arterial pressure and vascular resistance become even stronger, the noradrenaline content in the brain and myocardium and hyperglycaemia increase, and there is potentiation of the inhibitory effect of clonidine on electrically stimulated m.anococcygeus.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced; D001794:Blood Pressure; D003000:Clonidine / Q000009:adverse effects*; D006339:Heart Rate; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013564:Sympathetic Nervous System
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D003000:Clonidine