Regulation of hydraulic conductivity in response to sustained changes in pressure

The present study addresses the effect of a sustained change in pressure on microvascular permeability assessed by hydraulic conductivity (L-p) measurements from microvessels of the rat mesentery. With a microperfusion technique, transvascular filtration (normalized to surface area; J(v)/S) and L-p were measured in small arterioles (baseline Lp = 0.26 x 10(-7) cm (.) s(-1) (.) cmH(2)O(-1)) and venules (baseline Lp = 2.88 x 10(-7) cm (.) s(-1) (.) cmH(2)O(-1)). The main finding of this study is that step increases in microvascular pressure led to timedependent alterations of L-p. Immediately after a twofold step increase in pressure, J(v)/S increased in proportion to the pressure change. This observation is consistent with Starling's law that predicts filtration proportional to the overall pressure gradient when Lp is constant. However, when J(v)/S measurements continued for 60 - 90 min past the step in pressure, there was an initial decrease in J(v)/S for 30 min ( sealing effect) followed by a substantial increase in J(v)/S out to 90 min. The sustained increase in J(v)/S suggests an increase in L-p of 36 +/- 7% for small arterioles and 42 +/- 5% for small venules (P < 0.05 for both). In addition, the increase in L-p in response to an increase in pressure was attenuated significantly by nitric oxide synthase inhibition. These results indicate that a pressure-induced mechanical stimulus (possibly J(v)) activates a NO-dependent biochemical response that leads to an increase in hydraulic conductivity.