Facilitation of the release of noradrenaline: an extra-adrenal effect of adrenocorticotropic hormone.
Effects of ACTH-(1-24) on the release of noradrenaline from postganglionic sympathetic neurones were studied in rabbits. In the isolated perfused rabbit heart, ACTH-(1-24) (0.1-100 nmol/l) increased the overflow of noradrenaline elicited by sympathetic nerve stimulation at 1 Hz, an effect that persisted in the presence of propranolol and cocaine. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), ACTH-(1-24) (0.03-1 microgram/kg per min) increased the plasma noradrenaline concentration as well as the calculated rate of entry of noradrenaline into the plasma, but decreased arterial blood pressure by a direct vasodilator effect. In anaesthetized rabbits, ACTH-(1-24) (0.1-1 microgram/kg per min) also increased the plasma noradrenaline concentration; the higher dose in addition reduced the blood pressure and increased the firing rate of renal sympathetic nerves; however, the rise in plasma noradrenaline was greater than would have been expected from the increase in sympathetic firing rate alone. It is concluded that ACTH exerts two primary effects on the cardiovascular system of the rabbit: presynaptic facilitation of the noradrenaline release and postsynaptic vasodilation. The vasodilation leads to a baroreceptor-mediated reflex increase in sympathetic tone. The low concentrations of ACTH required suggest that presynaptic facilitation may occur in vivo, at least when the secretion of ACTH is high.
Szabo
B
B
Pharmakologisches Institut der Universität, Freiburg, F.R.G.
Hedler
L
L
Starke
K
K
D000320:Adrenergic Fibers / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006854:Hydrocortisone / Q000097:blood; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation; D009638:Norepinephrine / Q000097:blood*; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D003042:Cocaine; D003345:Corticosterone; D006854:Hydrocortisone; D009638:Norepinephrine