Loss of the effects of clonidine on the growth hormone release and hypotensive action in long-term castrated rats: the possible role of testosterone on alpha-2-adrenergic mechanisms of clonidine.
The effect of testosterone on the growth hormone (GH)-releasing and hypotensive actions of clonidine was evaluated in vivo using male Wistar rats. Clonidine at various doses and by various routes (5 micrograms/kg, i.c.v.; 15 micrograms/kg, i.v., and 7, 15, 31, 125 and 250 micrograms/kg, i.p.) induced a significant increase in plasma GH levels in rats. Intracerebroventricular (5 micrograms/kg) injection of clonidine significantly decreased blood pressure. The effects of clonidine on the GH release and blood pressure were lost in long-term castrated rats, but were restored by testosterone replacement in the castrates. In addition, the hypotensive response to clonidine in testosterone-replaced castrated rats lasted longer than in the sham-operated rats. The injection of yohimbine (3 mg/kg, i.p.) strongly inhibited the secretion of GH induced by clonidine treatment in sham-operated animals, and its inhibitory action was significantly attenuated in castrates. In long-term castrated rats, basal blood pressure decreased significantly compared with that of sham-operated rats. This was also restored after testosterone administration to castrates. The results of the present study indicate that the alpha 2-adrenergic receptor-mediated effects of clonidine on the GH release and blood pressure might be dependent on the endogenous testosterone secretion.
Kiem
D T
DT
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Stark
E
E
Fekete
M I
MI
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D013739:Testosterone; D013006:Growth Hormone; D003000:Clonidine