Microvascular permeability transients due to histamine in cat limb

We measured the protein solvent drag reflection coefficient (sigma f) and the capillary filtration coefficient (CFC) before and after adding 1 or 10 microM histamine to the recirculating fluid (20% plasma, remainder albumin and electrolytes, hematocrit of 1-2%) perfusing the isolated cat hindlimb preparation. Transient sigma f measurements were made at 3- to 15-min intervals after histamine using a modification of the steady-state integral-mass balance method. CFC measurements were made at approximately 10-min intervals after histamine in separate experiments. A 1 microM dose of histamine caused sigma f to fall from approximately 0.8 to approximately 0.3 in 2-3 min; sigma f then returned to control in approximately 20 min. CFC response to the 1 microM histamine was a peak increase approximately 2 times control and a return to control in approximately 40 min. A 10 microM dose caused sigma f to fall rapidly to near zero. In general, recovery was much slower than for the 1 microM dose, most of the limbs not returning to control by 40 min after histamine. CFC measurements after 10 microM histamine increased only approximately 5 times control even though sigma f was near zero at the same time. CFC remained above control for approximately 60 min. The combined sigma f and CFC data could be described quantitatively if histamine simultaneously opened both short-lived large gaps (approximately 1,000 A) and a longer-lived pathway that sieved protein like the normal pathway and if the numbers of channels of each pathway closed exponentially with 4- and 15-min time constants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)