Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline.
Isoprenaline bitartrate (0.5 microgram/kg/min i.v.) increased the rate of noradrenaline release into the circulation of pentobarbitone-anesthetized rabbits. This increase was much greater than that produced by an equi-hypotensive dose of the vasodilator hydralazine (0.2 mg/kg i.v.), suggesting that it was only partly due to baro-reflex activation of sympathetic nerves. This facilitatory effect of isoprenaline was also observed in the nephrectomized, pithed rabbit, with electrically stimulated sympathetic outflow, ruling out central nervous system and renin-angiotensin effects. ICI 118,551 HCl (0.3 mg/kg + 0.1 mg/kg/h i.v.) blocked the isoprenaline-induced hypotension, but did not affect the isoprenaline-induced tachycardia, suggesting that it selectively blocked beta 2-adrenoceptors. ICI 118,551 totally abolished the isoprenaline-induced increase in noradrenaline release, suggesting a beta 2-effect. Atenolol (0.3 mg/kg + 0.1 mg/kg/h) blocked the isoprenaline-induced tachycardia, a beta 1-effect, but only slightly attenuated the isoprenaline-induced increase in noradrenaline release. Atenolol by itself decreased heart rate and arterial pressure, but there was no reflex rise in the noradrenaline release rate, which suggests that atenolol impairs baroreceptor activation of sympathetic nerves. In another series of experiments, also in the pentobarbitone-anesthetized rabbit, adrenaline was released into the circulation by splanchnic nerve stimulation. This resulted in prolonged increases of adrenaline levels in heart tissue. After the plasma adrenaline levels had returned to prestimulation values, the rate of noradrenaline release into the plasma was enhanced. This increase was not observed in rabbits treated with either desipramine HCl (1 mg/kg i.v.) or propranolol HCl (2 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013153:Splanchnic Nerves / Q000502:physiology
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine