Constriction of isolated collecting lymphatic vessels in response to acute increases in downstream pressure

Abstract

Key points: Arterioles undergo a myogenic constriction, defined as a decrease in diameter in response to an increase in pressure, which serves to protect the downstream capillaries from changes in pressure and flow. A lymphatic constriction was recently identified but it remained unknown whether it reflected a true myogenic constriction. By selectively raising downstream pressure in isolated lymphatic vessels containing a single valve, we discovered that the upstream segment constricted, even when protected from increases in pressure by the closed valve. The constriction consisted of a myogenic component and a frequency component, which were blocked pharmacologically. The lymphatic constriction facilitated proper closure of the intraluminal valves in the face of a hydrostatic gradient, preventing lymph backflow. This work adds to our understanding of the lymphatic myogenic constriction by showing that it maintains a functioning valve system in lymphatic vessels and that it is mechanistically similar to the arteriolar myogenic constriction. Abstract Collecting lymphatic vessels generate pressure to transport lymph downstream to the subclavian vein against a significant pressure head. To investigate their response to elevated downstream pressure, collecting lymphatic vessels containing one valve (incomplete lymphangion) or two valves (complete lymphangion) were isolated from the rat mesentery and tied to glass cannulae capable of independent pressure control. Downstream pressure was selectively raised to various levels, either stepwise or ramp‐wise, while keeping upstream pressure constant. Diameter and valve positions were tracked under video microscopy, while intralymphangion pressure was measured concurrently with a servo‐null micropipette. Surprisingly, a potent lymphatic constriction occurred in response to the downstream pressure gradient due to (1) a pressure‐dependent myogenic constriction and (2) a frequency‐dependent decrease in diastolic diameter. The myogenic index of the lymphatic constriction (−3.3 ± 0.6, in mmHg) was greater than that of arterioles or collecting lymphatic vessels exposed to uniform increases in pressure (i.e. upstream and downstream pressures raised together). Additionally, the constriction was transmitted to the upstream lymphatic vessel segment even though it was protected from changes in pressure by a closed intraluminal valve; the conducted constriction was blocked by loading only the pressurized half of the vessel with either ML‐7 (0.5 m m) to block contraction, or cromakalim (3 μ m) to hyperpolarize the downstream muscle layer. Finally, we provide evidence that the lymphatic constriction is important to maintain normal intraluminal valve closure during each contraction cycle in the face of an adverse pressure gradient, which probably protects the lymphatic capillaries from lymph backflow.