Sensory nerves mediate neurogenic escape in rat gut

We investigated the involvement of primary sensory nerves in intestinal autoregulatory escape induced by postganglionic nerve stimulation (NS) in anesthetized rats. Anterior mesenteric artery (AMA) blood flow velocity (BF) was measured with a pulsed Doppler flowmeter. Periarterial NS elicited an abrupt fall in BF, which was followed by a recovery in BF toward the basal value, despite sustained NS. This recovery from NS constituted the neurogenic escape phenomenon. Vasoconstrictor responses to NS were abolished by periarterial application of tetrodotoxin. Acute, surgical interruption of proximal periarterial nerves had no effect on BF responses to distal NS, suggesting a peripheral rather than a central nervous mechanism for the escape phenomenon. Escape from NS-induced vasoconstriction was significantly inhibited by prior administration of the selective sensory neurotoxin capsaicin as either subcutaneous injection in neonatal life, acute application to periarterial nerves, or acute injection into the jejunal lumen. In rats pretreated 24 h with reserpine, NS provoked a vasodilator response that was inhibited by intrajejunal capsaicin. Increases in arterial blood pressure (BP) and heart rate observed during NS were blocked by periarterial (but not intrajejunal) application of capsaicin. Transmural electrical field stimulation elicited significantly greater nerve-induced contractions in AMA rings from control rats. Our findings support the hypothesis that postganglionic NS activates both vasoconstrictor sympathetic nerve branches and vasodilator afferent C-fibers. The latter nerves release vasodilator peptides in the periphery during continuous low frequency NS that appear to be essential for autoregulatory escaped in our model.