Intracerebroventricular administration of endothelins: effects on the supraspinal micturition reflex and blood pressure in the anaesthetized rat.
Intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 10 and 100 pmol/rat) or endothelin-3 (ET-3, 100 pmol/rat) inhibited the supraspinal micturition reflex (SMR) in urethane-anesthetized rats. Guanethidine pretreatment, vagotomy or forced ventilation did not modify the effect of i.c.v. ET-1 on the SMR. Intravenous (i.v.) administration of ET-1 (350 pmol/rat) also blocked the SMR with a delay of about 8 min. Guanethidine pretreatment revealed a stimulatory effect of i.v. ET-1 on the frequency of the SMR and the late inhibition was also reduced. In the isolated rat urinary bladder ET-1, ET-3 and ET-(16-21) induced a dose-related contraction and a small enhancement of the neurogenic contraction caused by electrical field stimulation. Inhibition of bladder motility by i.c.v. administration of ET-1 or ET-3 was paralleled by an increase in blood pressure. Both ET-1 and ET-3, at the same doses which evoked these autonomic effects, also killed some animals. The ET-1-induced increase in blood pressure was not prevented by guanethidine pretreatment or by spinal cord transection. Guanethidine pretreatment also did not modify the pressor response induced by i.v. ET-1. Bilateral cervical vagotomy enhanced the pressor response to i.c.v. ET-1. Forced ventilation prevented the death of some animals following i.c.v. administration of ET-1.
Lecci
A
A
Pharmacology Department, Menarini, Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Santicioli
P
P
Rovero
P
P
Maggi
C A
CA
Giachetti
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004558:Electric Stimulation; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006145:Guanethidine / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D012018:Reflex / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination
D016232:Endothelins; D006145:Guanethidine