ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at high pressure.

Most studies of neurovascular transmission in isolated small mesenteric arteries have used either isometric recording techniques or measured vasoconstriction in vessels with no distending pressure. Here we have used pressure myography to assess the contribution of noradrenaline and ATP to sympathetic neurotransmission in rat second-order mesenteric arteries. In arteries pressurized to 30 or 90 mmHg, activation of sympathetic axons with trains of electrical stimuli (50 pulses, 0.5-10 Hz) evoked frequency-dependent vasoconstrictions that increased in amplitude at higher pressure. In the presence of the P2-receptor antagonist suramin (0.1 mM), the amplitude of vasoconstrictions to trains at 2 and 10 Hz did not differ at 30 and 90 mmHg. In contrast, in the presence of the alpha(1)-adrenoceptor antagonist prazosin (0.1 microm) vasoconstrictions at 90 mmHg were larger than those at 30 mmHg. At both pressures, the combination of prazosin and suramin virtually abolished constrictions. The purinergic component of vasoconstriction (prazosin-resistant) was almost abolished by the L-type Ca(2+) channel antagonist nifedipine (1 microm). Increasing pressure from 30 to 90 mmHg decreased the resting membrane potential and increased the amplitude of purinergic excitatory junction potentials. These findings indicate that the contribution of ATP to neurovascular transmission increases when the pressure is raised from 30 to 90 mmHg, which is similar to the pressure second-order mesenteric arteries experience in vivo, and that Ca(2+) influx through L-type Ca(2+) channels is largely responsible for purinergic activation of the vascular smooth muscle.