Sympathetic neuromuscular transmission in rat tail artery: a study based on electrochemical, electrophysiological and...

The main purpose of the present thesis was to study sympathetic neuromuscular transmission at the varicosity level, in proximal regions of the isolated tail artery of 'adult' normotensive rat. The strategy was to compare the release and extracellular life-times of ATP and NA, as revealed by electrophysiological and electrochemical methods, respectively, with the contractile response to electrical field stimulation with a single pulse up to 20 min of stimulation at 20 Hz. The extracellularly recorded excitatory junction current (EJC) resolved, based on evidence in the literature, the quantal pulse-by-pulse release of ATP. The electrochemical signal, which reflected the rise and fall in the NA concentration at the surface of the carbon fibre electrode following nerve stimulation (termed delta[NA]CF), monitored on-line and 'in real time', the changes in the NA concentration at the surface of the artery. The total duration of the evoked EJC and delta[NA]CF responses indicated that the life-time of the ATP and NA released by a single pulse, or by short trains (10 pulses) at 50 Hz, was less than 100 ms or 3 sec, respectively. The corresponding contractile responses were mediated by both ATP (or a related nucleotide) and NA (but probably not NPY) via postjunctional P2x-purinoceptors, alpha 1- and alpha 2-adrenoceptors, respectively, and occurred with long delays during which the released ATP and NA had been virtually eliminated or removed from the respective receptors. The kinetics of these contractile responses are thus not determined by the duration of the presence of transmitters at the postjunctional receptors driving the contractions but by post-receptor mechanisms. The large differences in the time-course of these three components of the neurogenic contraction and the interaction between them reveal a novel, kinetic aspect of NA-ATP co-transmission. The relative contribution of NA and ATP to the neurogenic contraction and the relative role of components mediated via alpha 1- and alpha 2-adrenoceptors varied with the length and frequency of the stimulus trains. The ATP-mediated component of this response was always fast and normally small but could be powerful under certain conditions (e.g. in 'young' rats, or in the presence of K(+)-channel blocker). In addition, the results suggest that ATP released by field stimulation restricted both components of the NA-induced neurogenic contraction. The source(s) of the ATP exerting this inhibitory effect and the mechanisms of the inhibition are not clear at present.(ABSTRACT TRUNCATED AT 400 WORDS)