Capsaicin-sensitive nerves mediate inhibitory junction potentials and dilatation in guinea-pig mesenteric artery

1. The present study examined the effects of repetitive nerve stimulation on membrane potential and on contractile responses to noradrenaline in the guinea-pig inferior mesenteric artery and its distal branches. 2. Repetitive stimulation of perivascular nerves evoked slow inhibitory junction potentials (IJPs) and dilator responses. Individual nerve shocks elicited excitatory junction potentials (EJP)s. 3. Stimulation-evoked IJPs were abolished in the presence of tetrodotoxin (0.3 microM) or a low-Ca2+ (0.5 mM) superfusion solution. 4. The amplitudes and durations of IJPs were dependent on the frequency and duration of repetitive nerve stimulation. Nerve stimulation delivered at 5 Hz for 5 s induced IJPs which had an average amplitude of 2 mV and an average duration of 130 s. When the time interval between successive stimulation periods was less than 4 min, the amplitudes of IJPs were reduced in a time-dependent manner. 5. Stimulation-evoked IJPs were unaffected following endothelium removal. Furthermore, stimulation-evoked IJPs were not affected by atropine (1 microM), indomethacin (20 microM), prazosin (0.5 microM), phentolamine (10 microM), propranolol (0.5 microM) or alpha,beta-methylene ATP (0.2 microM). 6. Pre-treatment of arteries with guanethidine (30 microM) or 6-hydroxydopamine (0.4 mM) abolished stimulation-evoked EJPs but had no effect on stimulation-evoked IJPs. 7. In a similar manner to repetitive nerve stimulation, capsaicin (10 microM) itself induced membrane hyperpolarization and dilatation in mesenteric arteries. Moreover, following application of capsaicin (10 microM), stimulation-evoked IJPs and dilator responses were abolished. 8. EJPs evoked during stimulation-induced IJPs were reduced in amplitude, compared to EJPs evoked under resting conditions. 9. These findings suggest that, in addition to an excitatory sympathetic innervation, mesenteric arteries receive an inhibitory, capsaicin-sensitive innervation which is activated by low-frequency repetitive stimulation.