PREGANGLIONIC AND POSTGANGLIONIC STIMULATION-INDUCED NORADRENALINE OVERFLOW IS MARKEDLY FACILITATED BY A PREJUNCTIONAL BETA(2)-ADRENOCEPTOR-MEDIATED CONTROL MECHANISM IN THE PITHED RAT

The aim of the study was to further explore the prejunctional beta-adr enoceptor-mediated control mechanism of noradrenaline release from sym pathetic nerves in response to preganglionic nerve stimulation (PNS) a nd local nerve stimulation of the portal vein, respectively, in the pi thed rat. Baseline values as well as the increments of mean arterial b lood pressure (Delta-BP), heart rate (Delta-HR) and plasma noradrenali ne levels (Delta-NA) in response to four PNS episodes (0.8 Hz, 3 ms, 7 5 V for 45 s at 20 min intervals), respectively, were evaluated. Fenot erol administration (0.25 mg/kg, i.v.) reduced significantly the basal blood pressure but did not alter Delta-BP in response to PNS. Basal h eart rate markedly increased after fenoterol without any further chang e in heart rate induced by PNS. The beta(1)-selective antagonist CGP 2 0712A attenuated Delta-BP in response to PNS and prevented the fenoter ol-induced increase in basal heart rate. The beta(2)-selective antagon ist ICI 118,551 per se did not change the blood pressure and heart rat e values, but antagonized the fenoterol-induced decrease in basal bloo d pressure. Fenoterol enhanced plasma Delta-NA in response to PNS by 1 05% in comparison to the corresponding control value. This effect of f enoterol could be blocked by pretreatment with ICI 118,551 but not wit h CGP 20712A (a selective beta(1)-adrenoceptor antagonist) which per s e did not significantly change plasma Delta-NA. Repeated local stimula tion of the portal vein (S 1-S 3, 2 Hz, 3 ms, 10 mA, for 120 s at 30 m in intervals) increased portal plasma noradrenaline without changing m ean blood pressure and heart rate in pithed rats. Fenoterol enhanced t he increase in portal-vein plasma noradrenaline evoked by nerve stimul ation by 110%. Pretreatment with ICI 118,551 antagonized this effect o f fenoterol, but had per se no effect on the portal vein nerve stimula tion-evoked increase in portal plasma noradrenaline. It is concluded t hat the increase in plasma noradrenaline evoked both by pre- and postg anglionic nerve stimulation can be markedly enhanced by activation of a facilitatory prejunctional beta(2)-adrenoceptor control mechanism.