The effects of intermittent and continuous stimulation of microvessels in the cheek pouch of hamsters with histamine and bradykinin on the development of venular leaky sites.

: Continuous and intermittent stimulation of the hamster cheek pouch with either histamine or bradykinin was studied to evaluate microvascular permeability. Microscopy was accomplished by placing a chamber in the cheek pouch, suffusing the membrane with Ringer's bicarbonate (pH 7.4, 35 degrees C) and observing the microvessels with a Zeiss epistage microscope. Using FITC-dextran (MW 70,000) as the intravascular tracer, the number of leaky sites per cm2 tissue was quantitated before, during and after exposure to histamine (10(-5) M) or bradykinin (10(-7) M). Continuous superfusion with histamine or bradykinin for 60-90 minutes produced an increase in leaky sites which returned toward control during the superfusion. Intermittent stimulation with either histamine or bradykinin produced a maximal response which was not reduced by subsequent 30 minute pulses; whereas reducing the stimulus interval to 15 minutes led to a reduction in leaky sites on subsequent applications. After termination of continuous stimulation with either agent, the application of the other agent produced a response which was similar to the original. There was a minor reduction of responsiveness to intermittent applications of either histamine or bradykinin when the stimulus interval was greater than 15 minutes. These results support the concept of a receptor-mediated modulation of venular leaky sites.