NEURAL CONTROL OF THE ENDOCRINE RAT-HEART

Although atrial stretch is the accepted stimulus for atrial natriureti c factor (ANF), in vivo studies suggest a stretch-independent, neurall y induced ANF release mechanism. Thus the hypothesis that cardiac nerv es can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus wa s used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical s timulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropepti de Y in the effluent. ANF levels in the effluent increased by 120% ove r baseline with 0.5 muM scorpion venom and by 88% with 0.5 muM veratri dine (P < 0.01). Cardiac mechanics did not explain the large, concentr ation-dependent ANF response to the scorpion venom, since changes in t he left ventricular developed pressure were small, opposite to those i nduced by veratridine, and unaffected by sympathectomy or adrenergic r eceptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hard ly affected the ANF response to veratridine. Addition of 1 muM tetrodo toxin abolished an ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in conjunc tion with neuropeptide Y, whereas control stimulations were ineffectiv e. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion.