Davis MJ, Davis AM, Ku CW, Gashev AA. Myogenic constriction and dilation of isolated lymphatic vessels. Am J Physiol Heart Circ Physiol 296: H293-H302, 2009. First published November 21, 2008 doi:10.1152/ajpheart.01040.2008.-We tested the hypothesis that lymphatics would exhibit myogenic constrictions and dilations to intraluminal pressure changes. Collecting lymphatic vessels were isolated from rat mesentery, cannulated, and pressurized for in vitro study. The lymphatic diameter responses to controlled intraluminal pressure steps of different magnitudes were tested in the absence and presence of the inflammatory mediator substance P, which is known to enhance lymphatic contractility. Myogenic constriction, defined as a time-dependent decrease in end-diastolic diameter over a 1-to 2-min period following pressure elevation (after initial distension), was observed in the majority of rat mesenteric lymphatic vessels in vitro and occurred over a relatively wide pressure range (1-15 cmH 2O). Myogenic dilation, a time-dependent rise in end-diastolic diameter following pressure reduction, was observed in over half the vessels equilibrated at a low baseline pressure. Myogenic constrictions were independent of the cardiac-like and time-dependent compensatory decline in end-systolic diameter and increase in amplitude observed in almost all vessels following pressure elevation. Substance P increased the percentage of vessels exhibiting myogenic constriction, the magnitude and rate of constriction, and the pressure range over which constriction occurred. Our results demonstrate that myogenic responses occur in collecting lymphatic vessels and suggest that the response may aid in preventing vessel overdistension during inflammation/edema.

Phasic contractile activity in rat portal vein is more sensitive to the rate of change in length than to absolute length and this response is widely assumed to be a general characteristic of myogenic behaviour for vascular smooth muscle. Previously, we found that rat lymphatic vessels exhibit phasic contractile behaviour similar to that of portal vein. In the present study, we hypothesized that lymphatic muscle would exhibit rate-sensitive contractile responses to stretch. The hypothesis was tested on rat mesenteric lymphatics (90-220 μm, i.d.) using servo-controlled wire-and pressure-myograph systems to enable ramp increases in force or pressure at different rates. Under isometric conditions in wire-myograph preparations, both the amplitude and the frequency of phasic activity were enhanced at more optimal preloads, but superimposed upon this effect were bursts of contractions that occurred only during fast preload ramps. In such cases, the ratio of contraction frequency during the ramp to that at the subsequent plateau (at optimal preload) was > 1. Further, the frequency ratio increased as a function of the preload ramp speed, consistent with a rate-sensitive mechanism. In contrast, the amplitude ratio was < 1 and declined further with higher ramp speeds. Downward preload ramps produced corresponding rate-sensitive inhibition of contraction frequency but not amplitude. Similar findings were obtained in pressurized lymphatics in response to pressure ramps and steps. Our results suggest that lymphatics are sensitive to the rate of change in preload/pressure in a way that is different from portal vein, possibly because the pacemaker for generating electrical activity is rate sensitive but lymphatic muscle is not. The behaviour may be widely present in collecting lymphatic vessels and is probably an important mechanism for rapid adaptation of the lymphatic pump to local vascular occlusion. Phasic contractile activity of smooth muscle in rat portal vein is known to be more sensitive to the rate of change in length than to the absolute length (Johansson & Mellander, 1975). Under isometric conditions, the longitudinal muscle layer of portal vein exhibited spontaneous contractile activity that was superimposed on, and modulated by, the level of passive force (preload). When preload was elevated gradually from suboptimal to optimal level, large amplitude (AMP), high frequency (FREQ) contraction bursts were evident in the force recordings (Johansson & Mellander, 1975). The most prominent contraction bursts occurred just before and just after passive force reached a plateau at a more optimal preload. During the plateau, both AMP and FREQ This paper has online supplemental material. declined somewhat to values that were still higher than their respective values at the original (suboptimal) preload. Thus, the values of both AMP and FREQ were larger during the force ramp than at the higher, plateau level associated with a more optimal preload. Portal vein also exhibited the opposite response to reduction in preload: during ...

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Although rare, Exophiala species can cause exogenous endophthalmitis. Chronic endophthalmitis should be suspected in patients who develop persistent intraocular inflammation after infectious keratitis.

We report effects of adding insulin-like growth factor I (IGF-I) and methionyl human growth hormone (GH), alone or in combination, to adult bovine articular chondrocytes plated at high density. Purified human and synthetic IGF-I stimulated chondrocyte DNA and proteoglycan synthesis. GH had no effect on either process. However, GH added in combination with IGF-I increased proteoglycan, cell-associated proteoglycan, and keratan sulfate synthesis over levels observed with IGF-I alone. IGF-I and GH did not alter the hydrodynamic size of proteoglycans or synthesis of collagen. Our results show that GH and IGF-I act together to stimulate adult chondrocyte extracellular matrix synthesis.