A new method for simultaneous measurement of endogenous noradrenaline release and vascular responsiveness in perfused rabbit carotid arteries in vitro

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Abstract
1. A new preparation for large arteries was tested for the simultaneous measurement of noradrenaline release and vasoconstrictor response induced by nerve stimulation in vitro. 2. Preparations of rabbit carotid artery with an outflow cannula were perfused with a modified Krebs-Ringer bicarbonate solution containing propranolol (3 x 10(-6) M) and cocaine (10(-6) M), to block beta-adrenoceptors and uptake-1, respectively. 3. The perfused carotid arteries were subjected to both transmural field stimulations (TFS) and exogenous noradrenaline administrations. To evaluate the preparation, we carried out the procedures in two control groups and a group with yohimbine (10(-7) M) treatment, respectively. 4. TFS over the range of 1.5-24 Hz caused a frequency-dependent pressor response. Yohimbine significantly increased the TFS-induced pressor responses. 5. TFS also caused frequency-dependent endogenous noradrenaline release. The endogenous noradrenaline release was significantly enhanced by yohimbine treatment. When noradrenaline release was expressed as release per stimulus, it was frequency-dependent in the group with yohimbine treatment but not in control groups. 6. Exogenous noradrenaline induced a dose-dependent pressor response. The exogenous noradrenaline-induced vasoconstrictor response was significantly diminished by yohimbine treatment. 7. It is concluded that this preparation can be effectively used to study drug effects on noradrenergic neurotransmission in relatively large arteries under various pathophysiological states by simultaneously measuring catecholamine release and vascular responsiveness.