Evidence supporting the existence of presynaptic alpha-adrenoceptors in the regulation of endogenous noradrenaline release upon hepatic sympathetic nerve stimulation in the dog liver in vivo.
The existence and functional significance of presynaptic alpha-adrenoceptors within the liver was investigated in anesthetized dogs. The stimulation-evoked endogenous catecholamine overflow was determined in hepatic venous blood upon hepatic nerve stimulation (12 V, 1-8 Hz, 1 min). Under resting conditions, average plasma catecholamine levels in hepatic venous and aortic blood were 0.064 ng/ml and 0.334 ng/ml, respectively. A frequency-dependent increase (P less than 0.001) was found in the hepatic venous catecholamine overflow, while aortic catecholamine levels did not change significantly at any stimulation frequency tested. The increases in catecholamine overflow were associated with decreases in hepatic arterial vascular conductance (35-66%, P less than 0.001) at all frequencies tested. Yohimbine (0.3 mg/kg, i.v.) potentiated the catecholamine overflow by 110-140% (P less than 0.05) upon stimulation at low frequencies (1-4 Hz). Clonidine (20 micrograms/kg, i.v.) inhibited the catecholamine overflow by 55-76% (P less than 0.05) at frequencies of 1 and 2 Hz, and reduced the hepatic arterial response by 46% (P less than 0.01) at 1 Hz. The pretreatment with yohimbine (0.1 mg/kg, i.v.) abolished the inhibitory effects of clonidine both on the catecholamine overflow and the hepatic arterial responses. The results support the existence of a negative feedback mechanism mediated by presynaptic alpha-adrenoceptors in the local regulation of noradrenaline release from hepatic sympathetic fibers. A functional significance of this process was suggested by an improved correlation found in the presence of clonidine between the catecholamine overflow and the hepatic arterial vascular conductance.
D000818:Animals; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D008099:Liver / Q000294:innervation*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine