Smooth Muscle Mechanosensitivity Generates and Maintains Pressure Gradients Across the Intestine.

Abstract

Background: The gut, the ureter, or the Fallopian tube all transport biological fluids by generating trains of propagating smooth muscle constrictions collectively known as peristalsis. These tubes connect body compartments at different pressures. We extend here Poiseuille's experiments on liquid flow in inert tubes to an active, mechanosensitive tube: the intestine.

Methods: We use as a miniature myogenic peristaltic pump model, the fetal chicken gut, and measured the flow and contractile wave propagation as a function of the initially applied pressures and pressure gradients. We dissect the molecular pathways of smooth muscle mechanosensitivity by measuring the force generated by gut rings in different pharmacological conditions.

Results: We demonstrate that smooth muscle contractions in response to stretch or pressure is mediated by L-type Ca²⁺ channels and IP3 receptors. We show that this positive-feedback mechanosensitive behavior can spontaneously generate pressure gradients across gut segments initially subject to equal pressure; this same mechanism tends to stabilize initially applied pressure gradients; it can act jointly or compete with the pressure gradient induced by directional peristaltic waves. We demonstrate that high pressure differentials can reverse the physiological propagation direction of contractile waves imparted by interstitial cell of Cajal pacemaker activity. We find that flow rate increases with tube length, but that the maximum pressure differential generated depends solely on smooth muscle contractile force and on the initial resting pressure applied inside the organ.

Conclusions: We provide fundamental mechanical and hydrodynamic insight into the myogenic mechanisms of transport in the gastrointestinal tract. We scale up our results to other human peristaltic organs and discuss their implications for pathophysiology of intestinal obstruction, vesicoureteral reflux and endometriosis.