Effects of perfusion rate on permeability of frog and rat mesenteric microvessels to sodium fluorescein

The permeability, P-S, to sodium fluorescein (Stokes-Einstein radius = 0.45 nm) has been measured in single mesenteric capillaries of pithed frogs and anaesthetised rats as perfusion velocity, U, was varied over a range from 400 up to 2000-10 000 mum s(-1). P-S increased linearly with U. In 20 frog capillaries, mean (+/-S.E.M.) P-S (in mum s(-1)) = 9.35 (+/-1.55) U x 10(-5) + 0.244 (+/-0.0291). Similarly, in nine rat venules, mean P-S = 1.62 (+/-0.385) U x 10(-4) + 0.375 (+/-0.025). The flow-dependent component of permeability could be reversibly abolished in frog capillaries by superfusing with 100 muM noradrenaline and by superfusing rat venules with the nitric oxide synthase inhibitor, N-G-nitro-Larginine (20 muM). It was shown that changes in microvascular pressure accompanying changes in U during free perfusion could account for only 15 % of the changes in P-S, i.e. 85 % of the changes in PS were changes in the permeability coefficient itself. A comparison between the changes in P-S with U and the previously described changes in microvascular permeability to K+ with U, suggest that if the flow-dependent component of permeability is modelled as a population of pores of constant size, these have radii of 0.8 nm. Such a pathway would limit flow-dependent permeability to small hydrophilic molecules and have minimal effect on net fluid exchange.