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.