Peptidergic nerves mediate post-nerve stimulation hyperemia in rat gut

Abstract

Cessation of perivascular nerve stimulation (NS) elicits a transient increase in intestinal blood flow above the prestimulatory value. This enhancement of blood flow constitutes the phenomenon of post-nerve stimulation hyperemia (PSH). We investigated the involvement of peptidergic sensory nerves in intestinal PSH. In anesthetized rats the velocity of blood flowing through the anterior mesenteric artery (VBF) was measured with a pulsed Doppler velocimeter. PSH was induced by 4 min of postganglionic electrical NS (5 Hz). PSH was abolished by distal periarterial application of tetrodotoxin and intra-arterial lidocaine, which suggests a peripheral sensory nervous mechanism for PSH. The increase in conductance at peak PSH was blocked by pretreatment with the selective, primary afferent neurotoxin capsaicin administered as 1) subcutaneous injection in neonatal life, 2) topical application to periarterial nerves, or 3) injection into the jejunal lumen. In rats pretreated with reserpine, NS evoked a hyperemic response, which was blocked by capsaicin. Treatment with adenosine deaminase inhibited PSH considerably less than capsaicin, suggesting a lesser role for adenosine in PSH. Our findings support the hypothesis that postganglionic NS activates both adrenergic and peptidergic nerves and that the latter release vasodilator peptides in the gut during PSH.