Abstract

The influence of prejunctional beta adrenoceptors on neurotransmitter overflow from the sympathetic nerve terminals of the normotensive rat mesentery was investigated. The mesenteric vascular bed was isolated and perfused with Krebs-bicarbonate buffer containing phentolamine (10 microM), cocaine (10 microM) and corticosterone (40 microM). Periarterial nerve stimulation (2 Hz, 120 pulses) was performed at 8-min intervals. The influence of isoproterenol (ISO) on the stimulus-induced fractional overflow of norepinephrine (S-I OFLO) was determined by generating concentration-effect curves (0.1-1000 nM, 3- or 6.5-min exposure to each concentration). ISO did not significantly increase S-I OFLO at any concentration. On the contrary, there was a decrease in S-I OFLO at the highest concentration of ISO (1 microM). The time course of the actions of ISO was studied by utilizing single concentrations of ISO (10 nM or 1 microM, 6.5-min exposure). The presence of ISO did not significantly affect S-I OFLO at either concentration. However, S-I OFLO was decreased during stimulation periods after the removal of ISO (1 microM) from the perfusate. This inhibition was significantly attenuated by propranolol (1 microM). Pretreatment with the cyclooxygenase inhibitor indomethacin (2.8 microM) had no effect on the response to ISO or the inhibition observed after ISO removal. This inhibition remained sensitive to blockade by propranolol. Salbutamol (100 nM, 6.5-min exposure), a preferential beta 2 adrenoceptor agonist, did not facilitate or inhibit S-I OFLO. These data suggest that facilitatory prejunctional beta adrenoceptors are either not present or weakly coupled to their effector system in the normotensive rat mesentery.(ABSTRACT TRUNCATED AT 250 WORDS)