Inhibition of sympathetic nerve activity by acute administration of the tricyclic antidepressant desipramine.
In rats anesthetized with pentobarbital/chloral hydrate, the i.v. injection of desipramine (0.3 mg/kg) caused a rapid fall in mean arterial blood pressure accompanied by a reduction in efferent renal nerve integrated activity. A similar reduction in electrical activity was seen in the preganglionic splanchnic nerve. Pretreatment of the rats with yohimbine (0.3 mg/kg) increased renal nerve activity by 20%, and the decrease in blood pressure and renal nerve activity elicited by a subsequent dose of desipramine was blocked. I.v. injection of prazosin (0.05 mg/kg) caused a reduction in systemic blood pressure. The hypotensive effect of a subsequent dose of desipramine was largely blocked, whereas the fall in renal nerve activity was attenuated, but still present. The data are consistent with an action of desipramine to reduce central sympathetic tone by increasing the release of endogenous noradrenaline which acts on alpha 2-adrenoceptors at CNS sites controlling sympathetic activity. An additional involvement of central alpha 1-adrenoceptors cannot be ruled out.
Lavian
G
G
Rappaport Family Research Institute, Faculty of Medicine, Technion, Haifa, Israel.
Di Bona
G
G
Finberg
J P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D013153:Splanchnic Nerves / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003891:Desipramine; D011224:Prazosin