Modulation of sympathetic nerve activity by perivascular sensory nerves in the arterioles of the guinea-pig small intestine

Abstract

Objective: The aim of this study was to assess the role of perivascular sensory nerves in modulating constrictions of intestinal submucosal arterioles. Methods: Arteriole constrictions were induced either by nerve released adenosine 5′-triphosphate (ATP) or exogenous ATP or phenylephrine (PE). Individual nerve shocks were used to elicit excitatory junction potentials (EJPs) in the arteriole smooth muscle whereas trains of stimuli were used to evoke transient constrictions of the arteriole. Effects of the sensory neurotoxin, capsaicin, were examined on constrictions and EJPs. Results: Pre-treatment of the arteriole preparation with capsaicin did not cause any significant change in the amplitude of arteriole constrictions to exogenously applied ATP or PE. However, there was a significant increase in the amplitude of neurally evoked arteriole constrictions and EJPs, without a significant change in the decay time constant ( τ decay) of the EJPs. Exogenous application of calcitonin gene related peptide (CGRP) significantly decreased τ decay of the EJPs without affecting their amplitude, whereas substance P (SP) significantly decreased the amplitude of EJPs without affecting τ decay. Both, CGRP and SP, decreased the amplitude of neurally evoked and ATP induced constrictions. Whilst the inhibitory effects of CGRP on evoked and ATP induced constrictions were not significantly different, the reduction in evoked constrictions obtained with SP was significantly greater than the reduction in ATP induced constrictions. SP antagonist significantly increased the amplitude of neurally evoked constrictions. Conclusions: It is concluded that capsaicin-sensitive afferents inhibit the release of transmitter from perivascular sympathetic nerves via the prejunctional modulatory action of SP. The other putative sensory neurotransmitter, CGRP, appears to act postjunctionally on the arteriole smooth muscle.