Chronic clonidine treatment and its withdrawal: effects on blood pressure and catecholamine synthesizing enzymes in brain-stem nuclei.
We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.
Atkinson
J
J
Lambas-Senas
L
L
Parker
M
M
Boillat
N
N
Luthi
P
P
Sonnay
M
M
Seccia
M
M
Renaud
B
B
D000313:Adrenal Medulla / Q000201:enzymology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001933:Brain Stem / Q000201:enzymology*; D002395:Catecholamines / Q000096:biosynthesis*; D003000:Clonidine / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D004343:Drug Implants; D004435:Eating / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D004343:Drug Implants; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D003000:Clonidine