ATRIAL-NATRIURETIC-PEPTIDE NEGATIVELY MODULATES THE STIMULATORY EFFECTS OF ANGIOTENSIN-II ON TUBEROINFUNDIBULAR DOPAMINERGIC NEURONAL-ACTIVITY - NEUROCHEMICAL AND ELECTROPHYSIOLOGICAL STUDIES

The effects of angiotensin II (AII) and natriuretic peptide (ANP), alo ne or in combination, on tuberoinfundibular dopaminergic (TIDA) neuron al activity and on serum PRL levels were examined in this study. The T IDA neuronal activity was determined by measuring 3,4-dihydroxyphenyla cetic acid (DOPAC) concentration in the median eminence using high-per formance liquid chromatography plus electrochemical detection, and ser um PRL levels were determined by radioimmunoassay. Intracerebroventric ular injection of AII induced both time (5-60 min)- and dose (0.01-1 m u g)-dependent effects by stimulating TIDA neuronal activity and inhib iting serum PRL levels in ovariectomized, estrogen-treated rats. ANP i n 0.01-10 mu g doses, on the other hand, had no significant effect on TIDA neurons, nor on serum PRL at 30 min. When ANP (in 0.1-10 mu g dos es) was co-administered with AII (1 mu g dose), it dose-dependently at tenuated the effects of AII on TIDA neuronal activity and on serum PRL levels. In a separate study using single-unit recording of neurons of the dorsomedial arcuate nucleus (dmARC) in brain slices, where most T IDA neurons reside, AII stimulated 68.0% of 72 units recorded. Few (5. 6%) units were inhibited and the remaining ones were not responsive. A NP alone was mostly ineffective on dmARC neurons (63.0% of 54 units), and it stimulated and inhibited 22.2 and 14.8% of them, respectively. When ANP was co-administered with AII to AII-responsive units, however , it significantly attenuated the effects of AII in 81.5% of 27 units. Other neurons were unaffected. Thus, results from the in vivo study i ndicate that ANP can negatively modulate the stimulatory effect of AII on hypothalamic TIDA neurons and the inhibitory effect on serum PRL l evels; and the in vitro electrophysiological data substantiates this o bservation by showing that ANP exerts a similar modulation on dmARC ne urons.